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Sample records for antagonizes icp4-dependent silencing

  1. Silence multiple

    DEFF Research Database (Denmark)

    Søndergaard, Katia Dupret

    The article highlights the importance of silences in the processes of innovation in organizations, and the claim is that silence and the absence of talk distribute authority, responsibility and decisions. The act of silencing is conceptualised as a central “configurating actor”. Using an Actor-Ne...

  2. Gene Silencing

    Czech Academy of Sciences Publication Activity Database

    Kertbundit, Sunee; Juříček, Miloslav; Hall, T.C.

    Dordrecht : Springer, 2010 - (Jain, S.; Brar, D.), s. 631-652 ISBN 978-90-481-2966-9 Institutional research plan: CEZ:AV0Z50380511 Keywords : Gene Silencing * RISC complex Subject RIV: EB - Genetics ; Molecular Biology

  3. Silencing Near tRNA Genes Requires Nucleolar Localization*S

    OpenAIRE

    Wang, Li; Haeusler, Rebecca A.; Good, Paul D.; Thompson, Martin; Nagar, Sapna; Engelke, David R.

    2005-01-01

    Transcription by RNA polymerase II is antagonized by the presence of a nearby tRNA gene in Saccharomyces cerevisiae. To test hypotheses concerning the mechanism of this tRNA gene-mediated (tgm) silencing, the effects of specific gene deletions were determined. The results show that the mechanism of silencing near tRNA genes is fundamentally different from other forms of transcriptional silencing in yeast. Rather, tgm silencing is dependent on the ability to cluster the dispersed tRNA genes in...

  4. Silencing the city?

    OpenAIRE

    Jean-Paul Thibaud; Pascal Amphoux

    2013-01-01

    The notion of silence must be handled very carefully. In addition, its use reveals the way we deal with the urban environment as well as social life. What does the notion of silence convey about the current state of the urban sonic environment? How can we clarify the various meanings and the stakes involved in silence? Three themes are developed in order to answer these questions: silence as a research topic presents three complementary perspectives (acoustic, sociocultural, technological); s...

  5. Silencing the city?

    Directory of Open Access Journals (Sweden)

    Jean-Paul Thibaud

    2013-12-01

    Full Text Available The notion of silence must be handled very carefully. In addition, its use reveals the way we deal with the urban environment as well as social life. What does the notion of silence convey about the current state of the urban sonic environment? How can we clarify the various meanings and the stakes involved in silence? Three themes are developed in order to answer these questions: silence as a research topic presents three complementary perspectives (acoustic, sociocultural, technological; silence as a polysemous notion emphasises the ideas of keeping quiet, tranquillity and pause; silence as a design issue relies on basic properties and principles in order to orient the design of the urban sonic environment.

  6. Ombuds’ corner: Employee silence

    CERN Multimedia

    Vincent Vuillemin

    2013-01-01

    Although around a hundred cases a year are reported to the Ombuds, several issues may still not be disclosed due to employee silence*. The deliberate withholding of concerns, escalating misunderstandings or genuine conflicts can impede the global process of learning and development of a better respectful organizational workplace environment, and prevent the detection and correction of acts violating the CERN Code of Conduct.   For the employee him/herself, such silence can lead to feelings of anger, resentment, helplessness and humiliation. These feelings will inevitably contaminate personal and interpersonal relations, and poison creativity and effectiveness. Employee silence can be explained by many factors; sometimes it is connected to organizational forces. In their published paper*, authors Michael Knoll and Rolf van Dick found four forms of employee silence. People may stay silent if they feel that their opinion is neither welcomed nor valued by their management. They have gi...

  7. Memories Persist in Silence

    Directory of Open Access Journals (Sweden)

    Sandra Patricia Arenas Grisales

    2012-08-01

    Full Text Available This article exposes the hypothesis that memory artifacts, created to commemorate the victims of armed conflict in Colombia, are an expression of the underground memories and a way of political action in the midst of war. We analyze three cases of creations of memory artifacts in Medellín, Colombia, as forms of suffering, perceiving and resisting the power of armed groups in Medellín. The silence, inherent in these objects, should not be treated as an absence of language, but as another form of expression of memory. Silence is a tactic used to overcome losses and reset everyday life in contexts of protracted violence.

  8. Breaking the Silence

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    Many women who suffer from vaginitis have kept silent about their illness because they think it is shameful to have such a disease. The International Women’s Health Coalition (IWHC) has publicized the problem, referring to it as a "culture of silence"inherited from traditional thinking. The coalition has made attempts to improve women’s health conditions by changing people’s misconceptions about the disease. In 1997, under a grant from the American Ford Foundation, the Sichuan Provincial Women’s Federation carried out a study on women’s repro-ductive health, aimed at "breaking the silence."

  9. Stabilizing membrane domains antagonizes anesthesia

    CERN Document Server

    Machta, Benjamin B; Nouri, Mariam; McCarthy, Nicola L C; Gray, Erin M; Miller, Ann L; Brooks, Nicholas J; Veatch, Sarah L

    2016-01-01

    Diverse molecules induce general anesthesia with potency strongly correlated both with their hydrophobicity and their effects on certain ion channels. We recently observed that several anesthetics inhibit heterogeneity in plasma membrane derived vesicles by lowering the critical temperature ($T_c$) for phase separation. Here we exploit conditions that stabilize membrane heterogeneity to test the correlation between the anesthetic potency of n-alcohols and effects on $T_c$. First we show that hexadecanol acts oppositely to anesthetics on membrane mixing and antagonizes ethanol induced anesthesia in a tadpole behavioral assay. Second, we show that two previously described `intoxication reversers' raise $T_c$ in vesicles and counter ethanol's effects in vesicles, mimicking the findings of previous electrophysiological measurements. Third, we find that hydrostatic pressure, long known to reverse anesthesia, also raises $T_c$ in vesicles with a magnitude that counters the effect of an anesthetic at relevant concen...

  10. Illuminating employees’ organizational silence

    Directory of Open Access Journals (Sweden)

    Jaber Moghaddampour

    2013-08-01

    Full Text Available Undoubtedly, human capital is the main source of knowledge generation, which leads to a competitive advantage and sustainability of organizations. When managers pay more attention to such capital, they will be able to lead their organization, more effectively. In such route, the managers should look for their employees’ opinions on policies/plans of the organization and learn how to run the organization and organizational challenges. They should use their employees’ knowledge to improve the quality of decisions, they should encourage them to share their ideas and protect them from organizational silence. Thus, human capitals will be obviously considered as strategic capitals of an organization. Concerning the importance of organizational sound, the status of organizational silence is studied in 13 selected organizations in Qom Province – as one the biggest Iranian provinces. The findings indicate that organizational silence in Qom selected organizations is not in an ideal status and the current level should be mitigated. Likewise, findings show that there is no significant difference between organizational silence in Qom selected organizations in terms of demographic variables.

  11. Sexual and parental antagonism shape genomic architecture

    OpenAIRE

    Patten, Manus M.; Úbeda, Francisco; Haig, David

    2013-01-01

    Populations with two sexes are vulnerable to a pair of genetic conflicts: sexual antagonism that can arise when alleles have opposing fitness effects on females and males; and parental antagonism that arises when alleles have opposing fitness effects when maternally and paternally inherited. This paper extends previous theoretical work that found stable linkage disequilibrium (LD) between sexually antagonistic loci. We find that LD is also generated between parentally antagonistic loci, and b...

  12. Phenotypic spandrel: absolute discrimination and ligand antagonism

    OpenAIRE

    François, Paul; Johnson, Kyle A.; Saunders, Laura N.

    2015-01-01

    We consider the general problem of absolute discrimination between categories of ligands irrespective of their concentration. An instance of this problem is immune discrimination between self and not-self. We connect this problem to biochemical adaptation, and establish that ligand antagonism - the ability of sub threshold ligands to negatively impact response - is a necessary consequence of absolute discrimination.Thus antagonism constitutes a "phenotypic spandrel": a phenotype existing as a...

  13. Triclosan Antagonizes Fluconazole Activity against Candida albicans

    OpenAIRE

    Higgins, J.; Pinjon, E.; Oltean, H.N.; White, T. C.; Kelly, S.L.; Martel, C.M.; Sullivan, D. J.; Coleman, D C; MORAN, G.P

    2012-01-01

    Triclosan is a broad-spectrum antimicrobial compound commonly used in oral hygiene products. Investigation of its activity against Candida albicans showed that triclosan was fungicidal at concentrations of 16 mg/L. However, at subinhibitory concentrations (0.5-2 mg/L), triclosan antagonized the activity of fluconazole. Although triclosan induced CDR1 expression in C. albicans, antagonism was still observed in cdr1Δ and cdr2Δ strains. Triclosan did not affect fluconazole uptake or alter total ...

  14. Silence in Intercultural communication

    Institute of Scientific and Technical Information of China (English)

    Guo Jun

    2012-01-01

    In communication, most of people's attention focuses on verbal communication, nonverbal language as a means of exchange is often ignored. However, nonverbal language continues sending signals, and most of these signals are sent to conversational partners unconsciously. So correct understanding of these signals will help people improve effectiveness of communication. This article will focus on silence, a major part of nonverbal communication, exploring its communicative functions and cultural differences.

  15. The Conspiracy Of Silence

    OpenAIRE

    Cohen, Saul

    1980-01-01

    The issue of the impaired physician is compounded by not only mass denial of the problem, but also a 'conspiracy of silence' among many groups associated with the physician. The conspirators—including the physician himself, his family, community, professional colleagues and nurses as well as hospital boards and administration—are unable to reconcile deteriorating performance due to alcohol or drugs with an otherwise gifted professional who should know the dangers of substance abuse. They may ...

  16. The Silence of Michelangelo

    DEFF Research Database (Denmark)

    Foote, Jonathan

    2016-01-01

    In one of the many anecdotes about Michelangelo, the master neared completion of his colossal Moses, tapped him on the knee with his hammer and exclaimed,"Perché non parli?" As an act that liberates latent thoughts or material potentials, his cadenced hammer spoke through careful, repetitive, and...... understood as loud and distractive, instead activate a contemplative place of silence. Perhaps more than merely a tool for removing stone, the hammer was an instrument for sonorous meditation with materials and thinking....

  17. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied to...... mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how the...

  18. Gene silencing and homology-dependent gene silencing in Arabidopsis: genetic modifiers and DNA methylation.

    OpenAIRE

    Furner, I J; Sheikh, M. A.; Collett, C E

    1998-01-01

    Transgenes inserted into the plant genome can become inactive (gene silencing) or result in silencing of homologous cellular genes [homology-dependent gene silencing (HDG silencing)]. In an earlier study we reported HDG silencing of chalcone synthase (CHS) in Arabidopsis. This study concerns genetic revertants of one of the CHS HDG-silencing transgenic homozygotes. Two monogenic recessive trans-acting mutations (hog1 and ddm1) that impair gene silencing and HDG silencing were identified. Thes...

  19. Bodies, Spaces, Voices, Silences

    Directory of Open Access Journals (Sweden)

    Donatella Mazzoleni

    2013-07-01

    Full Text Available A good architecture should not only allow functional, formal and technical quality for urban spaces, but also let the voice of the city be perceived, listened, enjoyed. Every city has got its specific sound identity, or “ISO” (R. O. Benenzon, made up of a complex texture of background noises and fluctuation of sound figures emerging and disappearing in a game of continuous fadings. For instance, the ISO of Naples is characterized by a spread need of hearing the sound return of one’s/others voices, by a hate of silence. Cities may fall ill: illness from noise, within super-crowded neighbourhoods, or illness from silence, in the forced isolation of peripheries. The proposal of an urban music therapy denotes an unpublished and innovative enlarged interdisciplinary research path, where architecture, music, medicine, psychology, communication science may converge, in order to work for rebalancing spaces and relation life of the urban collectivity, through the care of body and sound dimensions.

  20. Silence Amenity Engineering

    Science.gov (United States)

    Fujita, Hajime

    Engineering civilization brought convenient and comfortable life to us. However, some environmental problems such as various pollutions have also been developed with it. Acoustical noise is one of the major problems in modern life. Noise is generated from a noise source and propagates through transmitting medium such as the air and eventually reaches a receiver, usually a human being. The noise problem can be avoided, therefore, if one of those three elements in the noise problem is removed completely. In actual case, engineers are looking for most efficient way combining the controls for these three elements. In this article, basic characteristics of noise is reviewed briefly at first, then sound field analysis to predict sound transmission is discussed Aerodynamic noise is one of the major problems in silence amenity engineering today. Basic concept of the aerodynamic noise generation mechanism is discussed in detail with applications to turbo-machinery and high speed train noise control technology.

  1. Agonism and antagonism at the insulin receptor

    DEFF Research Database (Denmark)

    Knudsen, Louise; Hansen, Bo Falck; Jensen, Pia; Pedersen, Thomas Åskov; Vestergaard, Kirsten; Schäffer, Lauge; Blagoev, Blagoy; Oleksiewicz, Martin B; Kiselyov, Vladislav V; De Meyts, Pierre Marcel Joseph

    2012-01-01

    insulin analogues. The occurrence of ligand agonism and antagonism is well described for G protein-coupled receptors (GPCRs) and other receptors but in general, with the exception of antibodies, not for receptor tyrosine kinases (RTKs). In the case of the IR, no natural ligand or insulin analogue has been...

  2. RNA silencing movement in plants

    Institute of Scientific and Technical Information of China (English)

    Glykeria Mermigka; Frederic Verret; Kriton Kalantidis

    2016-01-01

    Multicellular organisms, like higher plants, need to coordinate their growth and development and to cope with environmental cues. To achieve this, various signal molecules are transported between neighboring cells and distant organs to control the fate of the recipient cells and organs. RNA silencing produces cell non-autonomous signal molecules that can move over short or long distances leading to the sequence specific silencing of a target gene in a well defined area of cells or throughout the entire plant, respectively. The nature of these signal molecules, the route of silencing spread, and the genes involved in their production, movement and reception are discussed in this review. Additionally, a short section on features of silencing spread in animal models is presented at the end of this review.

  3. Identification and mechanism of ABA receptor antagonism

    Energy Technology Data Exchange (ETDEWEB)

    Melcher, Karsten; Xu, Yong; Ng, Ley-Moy; Zhou, X. Edward; Soon, Fen-Fen; Chinnusamy, Viswanathan; Suino-Powell, Kelly M; Kovach, Amanda; Tham, Fook S.; Cutler, Sean R.; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang; Xu, H. Eric (NU Sinapore); (Van Andel); (UCR)

    2010-11-11

    The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands.

  4. Price Variation Antagonism and Firm Pricing Policies

    OpenAIRE

    Courty, Pascal; Pagliero, Mario

    2010-01-01

    Abstract Pricing schemes that vary prices in response to demand shocks may antagonize consumers and reduce demand. At the same time, consumers may take advantage of the opportunities offered by price changes. Overall, the net impact of varying price on demand is ambiguous. We investigate this issue empirically, exploiting a unique dataset from a firm that has experimented with different pricing schemes. Each scheme is characterized by how much prices respond to fluctuations in dema...

  5. Price Variation Antagonism and Firm Pricing Policies

    OpenAIRE

    Pascal Courty; Mario Pagliero

    2010-01-01

    Pricing schemes that vary prices in response to demand shocks may antagonize consumers and reduce demand. At the same time, consumers may take advantage of the opportunities offered by price changes. Overall, the net impact of varying price on demand is ambiguous. We investigate this issue empirically, exploiting a unique dataset from a firm that has experimented with different pricing schemes. Each scheme is characterized by how much prices respond to fluctuations in demand and generates dif...

  6. Triclosan antagonizes fluconazole activity against Candida albicans.

    LENUS (Irish Health Repository)

    Higgins, J

    2012-01-01

    Triclosan is a broad-spectrum antimicrobial compound commonly used in oral hygiene products. Investigation of its activity against Candida albicans showed that triclosan was fungicidal at concentrations of 16 mg\\/L. However, at subinhibitory concentrations (0.5-2 mg\\/L), triclosan antagonized the activity of fluconazole. Although triclosan induced CDR1 expression in C. albicans, antagonism was still observed in cdr1Δ and cdr2Δ strains. Triclosan did not affect fluconazole uptake or alter total membrane sterol content, but did induce the expression of FAS1 and FAS2, indicating that its mode of action may involve inhibition of fatty acid synthesis, as it does in prokaryotes. However, FAS2 mutants did not exhibit increased susceptibility to triclosan, and overexpression of both FAS1 and FAS2 alleles did not alter triclosan susceptibility. Unexpectedly, the antagonistic effect was specific for C. albicans under hypha-inducing conditions and was absent in the non-filamentous efg1Δ strain. This antagonism may be due to the membranotropic activity of triclosan and the unique composition of hyphal membranes.

  7. WIF1 is a frequent target for epigenetic silencing in squamous cell carcinoma of the cervix

    OpenAIRE

    Delmas, Amber L.; Riggs, Bridget M; Pardo, Carolina E.; Dyer, Lisa M.; Darst, Russell P.; Izumchenko, Eugene G.; Monroe, Mänette; Hakam, Ardeshir; Kladde, Michael P.; Erin M Siegel; Brown, Kevin D.

    2011-01-01

    Aberrant activation of the Wnt/β-catenin signaling axis is a prominent oncogenic mechanism in numerous cancers including cervical cancer. Wnt inhibitory factor-1 (WIF1) is a secreted protein that binds Wnt and antagonizes Wnt activity. While the WIF1 gene is characterized as a target for epigenetic silencing in some tumor types, WIF1 expression has not been examined in human cervical tissue and cervical cancer. Here, we show that WIF1 is unmethylated and its gene product is expressed in norma...

  8. Natural Protection of Wood with Antagonism Fungi

    Directory of Open Access Journals (Sweden)

    Alba ZAREMSKI

    2011-03-01

    Full Text Available Biological environments contain a certain number of microbial populations which, within a givenecological niche, display various relations ranging from symbiosis to parasitism. Researchers have beeninterested in these types of relations for around fifty years, especially in one very particular type ofrelationship: the antagonism exerted between individuals of the same microbial population.Today, the role played by biological agents, bringing into play inhibitive or destructive antibioticsubstances, reveals a certain potential for their use in controlling microorganisms associated with suchdegradation processes.The work undertaken by HydroQuébec and CIRAD involved two types of experiment: 1 in Petri dishes toassess and characterize the antagonistic capacity of Trichoderma against white rot and brown rot fungi; 2on pieces taken from untreated poles in order to study confrontation between the basidiomycete and theantagonistic strain in wood.This study investigated the antagonism of three ascomycetes of the genus Trichoderma against two whiterot basidiomycetes, Pycnoporus sanguineus and Coriolus versicolor, and two brown rot basidiomycetes,Antrodia sp. and Coniophora puteana, through direct confrontation in Petri dishes and in the wood ofHydroQuébec poles.The results obtained seemed to complete each other coherently. They revealed that the Trichodermagroup of fungi was not aggressive to wood and the results obtained after direct confrontation in Petri disheswere confirmed in wood.By directly exposing the different basidiomycetes and antagonists to each other in Petri dishes, two bytwo, we effectively revealed an antagonism effect for a large majority of the pairs. However, there wassubstantial variability in reactions from one pair to the next.

  9. Identification and mechanism of ABA receptor antagonism

    KAUST Repository

    Melcher, Karsten

    2010-08-22

    The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.

  10. Communicative Silences: Forms and Functions

    Science.gov (United States)

    Bruneau, Thomas J.

    1973-01-01

    The nature of silence is discussed as an imposition of mind, as an interdependent signification ground for speech signs, as a relationship to mental time (as opposed to artificial time), and as it relates to sensation, perception and metaphorical movement. (Author)

  11. Teaching Note: Gaining Voice through Silence

    Science.gov (United States)

    Kaufman, Peter

    2008-01-01

    For educators striving to create an egalitarian classroom based on open, reflexive, and honest dialogue, silence can be the ultimate obstacle. Not only does silence stifle individual expression; more importantly, silence also prevents the collective production of knowledge, understanding, compassion, and empathy. When learners and teachers feel…

  12. Rotavirus Antagonism of the Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Michelle M. Arnold

    2009-11-01

    Full Text Available Rotavirus is a primary cause of severe dehydrating gastroenteritis in infants and young children. The virus is sensitive to the antiviral effects triggered by the interferon (IFN-signaling pathway, an important component of the host cell innate immune response. To counteract these effects, rotavirus encodes a nonstructural protein (NSP1 that induces the degradation of proteins involved in regulating IFN expression, such as members of the IFN regulatory factor (IRF family. In some instances, NSP1 also subverts IFN expression by causing the degradation of a component of the E3 ubiquitin ligase complex responsible for activating NF-κB. By antagonizing multiple components of the IFN-induction pathway, NSP1 aids viral spread and contributes to rotavirus pathogenesis.

  13. Theophylline antagonizes diazepam-induced psychomotor impairment.

    Science.gov (United States)

    Henauer, S A; Hollister, L E; Gillespie, H K; Moore, F

    1983-01-01

    Eight healthy men received an oral dose of 0.25 mg/kg diazepam followed 40 min later by an intravenous infusion of 100 ml physiological sodium chloride solution, with or without 4.4 mg/kg theophylline. Psychomotor function was assessed after each blood sampling up to 5 h post-infusion. Thirty min after diazepam psychomotor performance measured by Card Sorting test and Digit Symbol Substitution test was impaired and subjects felt sleepy and could think less clearly (two factors of the Clyde Mood Scale). Theophylline antagonized the diazepam-induced impairment statistically significantly for up to 5 h and subjects felt less tense and less apprehensive (State Anxiety Inventory). Since pharmacokinetic parameters of diazepam seemed not to be different after theophylline, interaction at receptor level can be assumed. PMID:6662173

  14. Transcriptional Silencing of Retroviral Vectors

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M.; Pedersen, F.S.

    1996-01-01

    Although retroviral vector systems have been found to efficiently transduce a variety of cell types in vitro, the use of vectors based on murine leukemia virus in preclinical models of somatic gene therapy has led to the identification of transcriptional silencing in vivo as an important problem....... Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral...... transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the t...

  15. Polycomb complexes and silencing mechanisms

    DEFF Research Database (Denmark)

    Lund, Anders H; van Lohuizen, Maarten

    2004-01-01

    Advances in the past couple of years have brought important new knowledge on the mechanisms by which Polycomb-group proteins regulate gene expression and on the consequences of their actions. The discovery of histone methylation imprints specific for Polycomb and Trithorax complexes has provided...... mechanistic insight on how this ancient epigenetic memory system acts to repress and indicates that it may share mechanistic aspects with other silencing and genome-protective processes, such as RNA interference....

  16. Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1

    Directory of Open Access Journals (Sweden)

    Yu Lianbo

    2011-05-01

    Full Text Available Abstract Background MicroRNA (miRNA-mediated RNA silencing is integral to virtually every cellular process including cell cycle progression and response to virus infection. The interplay between RNA silencing and HIV-1 is multifaceted, and accumulating evidence posits a strike-counterstrike interface that alters the cellular environment to favor virus replication. For instance, miRNA-mediated RNA silencing of HIV-1 translation is antagonized by HIV-1 Tat RNA silencing suppressor activity. The activity of HIV-1 accessory proteins Vpr/Vif delays cell cycle progression, which is a process prominently modulated by miRNA. The expression profile of cellular miRNA is altered by HIV-1 infection in both cultured cells and clinical samples. The open question stands of what, if any, is the contribution of Tat RNA silencing suppressor activity or Vpr/Vif activity to the perturbation of cellular miRNA by HIV-1. Results Herein, we compared the perturbation of miRNA expression profiles of lymphocytes infected with HIV-1NL4-3 or derivative strains that are deficient in Tat RNA silencing suppressor activity (Tat K51A substitution or ablated of the vpr/vif open reading frames. Microarrays recapitulated the perturbation of the cellular miRNA profile by HIV-1 infection. The miRNA expression trends overlapped ~50% with published microarray results on clinical samples from HIV-1 infected patients. Moreover, the number of miRNA perturbed by HIV-1 was largely similar despite ablation of Tat RSS activity and Vpr/Vif; however, the Tat RSS mutation lessened HIV-1 downregulation of twenty-two miRNAs. Conclusions Our study identified miRNA expression changes attributable to Tat RSS activity in HIV-1NL4-3. The results accomplish a necessary step in the process to understand the interface of HIV-1 with host RNA silencing activity. The overlap in miRNA expression trends observed between HIV-1 infected CEMx174 lymphocytes and primary cells supports the utility of cultured

  17. [A gun silencer of a special kind].

    Science.gov (United States)

    Schyma, C; Schyma, P; Milbradt, H

    2000-01-01

    The authors report about a small bore pistol with silencer. In addition, the silencer can be sealed up by a rubber plate. This leads to a false estimation of the shooting distance. Also at close range shots the shot with the silencer and the rubber seal leaves hardly gunshot residues. The bullet wipe persists but microradiography shows his changed morphological composition. The use of the rubber seal leads predominantly to atypical bullet holes. PMID:10829239

  18. Real Right Alternation and Its Adversarial Problem Under Registration Antagonism

    OpenAIRE

    Yaqi HU

    2014-01-01

    With the continuous development of socialist market economy in China, real right alternation has become increasingly frequent, which is becoming the critical issue in the legislation of real right. In this legislation, a binary structure model has been adopted by China, which is based on registration essentials doctrine and supplemented by registration antagonism. This paper describes the registration antagonism in the real right alternation, and studies its adversarial problems.

  19. [E. M. Jellinek's silenced and silencing transgenerational story].

    Science.gov (United States)

    Kelemen, Gábor; Márk, Mónika

    2013-01-01

    Jellinek is a kind of archetypal character for future generations in the field of addiction studies. His implosion in the arena of alcoholism around the age of 50 was an unexpected challenge to medical science. We know very little about his own role models giving an intellectual and moral compass to his pragmatic creativity. More than 30 years has passed since Jellinek's death when an American sociologist Ron Roizen started unearthing his silent story. Roizen discerned that there are a lot of unsaid and muted issues in his personal Hungarian past. Our paper, based on the authors' research in Hungarian archives and other sources reveals that not just Jellinek's personal but his transgenerational narrative has been not-yet-said. This silenced and silencing history appears an unfinished business of acculturation of the family, which started prior to four generations. Authors have been concluding that the issue of religious conversion is a critical point in the process of acculturation. They examine the counter move of loyalty to family values and driving force of assimilation making their story unspeakable. PMID:24443572

  20. Dissection of Silencing Signal Movement in Arabidopsis

    OpenAIRE

    Smith, Lisa M.; Baulcombe, David C.

    2007-01-01

    In our recent paper in Plant Cell, we examined the phenomenon of non-cell autonomous RNA silencing through a genetic screen of the requirements for cell-to-cell signal movement.1 We found a requirement for components of the nuclear and trans-acting RNA silencing pathways in blocking or enhancing the spread of silencing and identified a new SNF2 domain-containing protein, CLSY1, in the nuclear RNA silencing pathway. Here we discuss our data from a broader perspective of other recently publishe...

  1. A Strategy for Antagonizing Quorum Sensing

    Energy Technology Data Exchange (ETDEWEB)

    G Chen; L Swem; D Swem; D Stauff; C OLoughlin; P Jeffrey; B Bassler; F Hughson

    2011-12-31

    Quorum-sensing bacteria communicate via small molecules called autoinducers to coordinate collective behaviors. Because quorum sensing controls virulence factor expression in many clinically relevant pathogens, membrane-permeable quorum sensing antagonists that prevent population-wide expression of virulence genes offer a potential route to novel antibacterial therapeutics. Here, we report a strategy for inhibiting quorum-sensing receptors of the widespread LuxR family. Structure-function studies with natural and synthetic ligands demonstrate that the dimeric LuxR-type transcription factor CviR from Chromobacterium violaceum is potently antagonized by molecules that bind in place of the native acylated homoserine lactone autoinducer, provided that they stabilize a closed conformation. In such conformations, each of the two DNA-binding domains interacts with the ligand-binding domain of the opposing monomer. Consequently, the DNA-binding helices are held apart by {approx}60 {angstrom}, twice the {approx}30 {angstrom} separation required for operator binding. This approach may represent a general strategy for the inhibition of multidomain proteins.

  2. The RNA-induced Silencing Complex: A Versatile Gene-silencing Machine*

    OpenAIRE

    Pratt, Ashley J.; MacRae, Ian J.

    2009-01-01

    RNA interference is a powerful mechanism of gene silencing that underlies many aspects of eukaryotic biology. On the molecular level, RNA interference is mediated by a family of ribonucleoprotein complexes called RNA-induced silencing complexes (RISCs), which can be programmed to target virtually any nucleic acid sequence for silencing. The ability of RISC to locate target RNAs has been co-opted by evolution many times to generate a broad spectrum of gene-silencing pathways. Here, we review t...

  3. Extremely stable Piwi-induced gene silencing in Caenorhabditis elegans

    OpenAIRE

    Luteijn, Maartje J.; van Bergeijk, Petra; Kaaij, Lucas J. T.; Almeida, Miguel Vasconcelos; Roovers, Elke F.; Berezikov, Eugene; Ketting, René F.

    2012-01-01

    RNA-induced epigenetic silencing (RNAe) is a new pathway in C. elegans initiated by the Piwi protein PRG-1. RNAe stably silences transgenes over many generations through a nuclear RNAi pathway that induces transcriptional silencing.

  4. Silence in Cross-cultural Communication

    Institute of Scientific and Technical Information of China (English)

    常利娜; 郭芳芳; 郝继亭; 顾庆媛; 孙胜强

    2008-01-01

    In academic field, silence is classified as part of the nonverbal communication. Edward T. Hall regarded silence as a key standard of dividing high-context cultures and low-context cultures (毕 46). In high-context cultures, information is provided through gestures, the use of space, and even silence. Little information is explicitly explained by words. Chinese, Japanese, Native American cultures are high-context ones. However, "in low-context cultures, the verbal message contains most of the information and very little is embedded in the context." (Samovar, A. Larry, Richard E. Porter and Lisa A. Stefani 79). How do people from different cultures respond to silence? How their values affect their attitudes? What causes silence?

  5. Mammalian meiotic silencing exhibits sexually dimorphic features.

    Science.gov (United States)

    Cloutier, J M; Mahadevaiah, S K; ElInati, E; Tóth, A; Turner, James

    2016-06-01

    During mammalian meiotic prophase I, surveillance mechanisms exist to ensure that germ cells with defective synapsis or recombination are eliminated, thereby preventing the generation of aneuploid gametes and embryos. Meiosis in females is more error-prone than in males, and this is in part because the prophase I surveillance mechanisms are less efficient in females. A mechanistic understanding of this sexual dimorphism is currently lacking. In both sexes, asynapsed chromosomes are transcriptionally inactivated by ATR-dependent phosphorylation of histone H2AFX. This process, termed meiotic silencing, has been proposed to perform an important prophase I surveillance role. While the transcriptional effects of meiotic silencing at individual genes are well described in the male germ line, analogous studies in the female germ line have not been performed. Here we apply single- and multigene RNA fluorescence in situ hybridization (RNA FISH) to oocytes from chromosomally abnormal mouse models to uncover potential sex differences in the silencing response. Notably, we find that meiotic silencing in females is less efficient than in males. Within individual oocytes, genes located on the same asynapsed chromosome are silenced to differing extents, thereby generating mosaicism in gene expression profiles across oocyte populations. Analysis of sex-reversed XY female mice reveals that the sexual dimorphism in silencing is determined by gonadal sex rather than sex chromosome constitution. We propose that sex differences in meiotic silencing impact on the sexually dimorphic prophase I response to asynapsis. PMID:26712235

  6. The gifts of silence and solitude.

    Science.gov (United States)

    Schmidt Bunkers, Sandra

    2008-01-01

    In this column the author describes the importance of finding silence and solitude amid the noise and technology present today in the teaching-learning academy. Three gifts of silence and solitude are identified: the gift of comforting aloneness, the gift of vision for new horizons, and the gift of a sense of freedom. A humanbecoming perspective is used to explore the implications of these gifts. This column introduces a column by Diana Vander Woude describing her teaching-learning experience in leadership focusing on silence and solitude. PMID:18096981

  7. Titration and hysteresis in epigenetic chromatin silencing

    International Nuclear Information System (INIS)

    Epigenetic mechanisms of silencing via heritable chromatin modifications play a major role in gene regulation and cell fate specification. We consider a model of epigenetic chromatin silencing in budding yeast and study the bifurcation diagram and characterize the bistable and the monostable regimes. The main focus of this paper is to examine how the perturbations altering the activity of histone modifying enzymes affect the epigenetic states. We analyze the implications of having the total number of silencing proteins, given by the sum of proteins bound to the nucleosomes and the ones available in the ambient, to be constant. This constraint couples different regions of chromatin through the shared reservoir of ambient silencing proteins. We show that the response of the system to perturbations depends dramatically on the titration effect caused by the above constraint. In particular, for a certain range of overall abundance of silencing proteins, the hysteresis loop changes qualitatively with certain jump replaced by continuous merger of different states. In addition, we find a nonmonotonic dependence of gene expression on the rate of histone deacetylation activity of Sir2. We discuss how these qualitative predictions of our model could be compared with experimental studies of the yeast system under anti-silencing drugs. (paper)

  8. AOP description: ER antagonism leading to reproductive dysfunction (in fish)

    Science.gov (United States)

    This adverse outcome pathway details the linkage between antagonism of estrogen receptor in females and the adverse effect of reduced cumulative fecundity in repeat-spawning fish species. Cumulative fecundity is the most apical endpoint considered in the OECD 229 Fish Short Term ...

  9. ANDROGEN RECEPTOR ANTAGONISM BY THE ORGANOPHOSPHATE INSECTICIDE FENITROTHION

    Science.gov (United States)

    Androgen receptor antagonism by the organophosphate insecticide fenitrothion. Tamura, H., Maness, S.C., Reischmann, K. Dorman, D.C., Gray, L.E., and Gaido, K.W. (2000). Toxicol. Sci. Organophosphate insecticides represent one of the most widely used classes of pesticide...

  10. Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism

    Directory of Open Access Journals (Sweden)

    Kerstin Gnirß

    2014-04-01

    Full Text Available The host cell protein tetherin can restrict the release of enveloped viruses from infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane domains of Vpu and tetherin. In contrast, the glycoproteins (GPs of two filoviruses, Ebola and Marburg virus, antagonize tetherin without reducing surface expression, and the domains in GP required for tetherin counteraction are unknown. Here, we show that filovirus GPs depend on the presence of their authentic transmembrane domains for virus-cell fusion and tetherin antagonism. However, conserved residues within the transmembrane domain were dispensable for membrane fusion and tetherin counteraction. Moreover, the insertion of the transmembrane domain into a heterologous viral GP, Lassa virus GPC, was not sufficient to confer tetherin antagonism to the recipient. Finally, mutation of conserved residues within the fusion peptide of Ebola virus GP inhibited virus-cell fusion but did not ablate tetherin counteraction, indicating that the fusion peptide and the ability of GP to drive host cell entry are not required for tetherin counteraction. These results suggest that the transmembrane domains of filoviral GPs contribute to tetherin antagonism but are not the sole determinants.

  11. Exploitative and hierarchical antagonism in a cooperative bacterium.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available Social organisms that cooperate with some members of their own species, such as close relatives, may fail to cooperate with other genotypes of the same species. Such noncooperation may take the form of outright antagonism or social exploitation. Myxococcus xanthus is a highly social prokaryote that cooperatively develops into spore-bearing, multicellular fruiting bodies in response to starvation. Here we have characterized the nature of social interactions among nine developmentally proficient strains of M. xanthus isolated from spatially distant locations. Strains were competed against one another in all possible pairwise combinations during starvation-induced development. In most pairings, at least one competitor exhibited strong antagonism toward its partner and a majority of mixes showed bidirectional antagonism that decreased total spore production, even to the point of driving whole populations to extinction. Differential response to mixing was the primary determinant of competitive superiority rather than the sporulation efficiencies of unmixed populations. In some competitive pairings, the dominant partner sporulated more efficiently in mixed populations than in clonal isolation. This finding represents a novel form of exploitation in bacteria carried out by socially competent genotypes and is the first documentation of social exploitation among natural bacterial isolates. Patterns of antagonistic superiority among these strains form a highly linear dominance hierarchy. At least some competition pairs construct chimeric, rather than segregated, fruiting bodies. The cooperative prokaryote M. xanthus has diverged into a large number of distinct social types that cooperate with clone-mates but exhibit intense antagonism toward distinct social types of the same species. Most lengthy migration events in nature may thus result in strong antagonism between migratory and resident populations, and this antagonism may have large effects on local

  12. Spatial and temporal dynamics of the RNA silencing response

    OpenAIRE

    Groenenboom, M.A.C.

    2008-01-01

    In this thesis we studied various aspects of siRNA mediated silencing. siRNA mediated silencing is initiated by the introduction of dsRNA, transgenes and viral infection. Our first goal was to study the ability of the core pathway of RNA silencing to explain transgene and dsRNA induced silencing. To that extend we developed and studied concise models of the RNA silencing pathway. Secondly, we investigated the efficacy of RNA silencing to reduce viral infections, and added a replicating RNA vi...

  13. The Hedgehog inhibitor cyclopamine antagonizes chemoresistance of breast cancer cells

    OpenAIRE

    Chai F; Zhou J; Chen C; Xie S; Chen X.; Su P; Shi J

    2013-01-01

    Feng Chai,1 Jiangang Zhou,1 Cheng Chen,1 Song Xie,2 Xiao Chen,1 Ping Su,3 Jun Shi3 1Oncology Department, 2General Surgery Department, 3Hematology Department, Zhejiang Xiaoshan Hospital, Hangzhou, People's Republic of China Abstract: Chemoresistance of cancer cells has been a severe problem in multiple types of cancers. One possibility is to combine different drugs with chemotherapy for improved efficacy. Cyclopamine blocks Hedgehog signaling by antagonizing Smo function, which induce...

  14. CXCR4 Antagonism Attenuates the Development of Diabetic Cardiac Fibrosis.

    Directory of Open Access Journals (Sweden)

    Po-Yin Chu

    Full Text Available Heart failure (HF is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice or type II diabetes (Israeli Sand-rats and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach.

  15. Nucleolar dominance and ribosomal RNA gene silencing

    OpenAIRE

    Tucker, Sarah; Vitins, Alexa; Pikaard, Craig S.

    2010-01-01

    Nucleolar dominance is an epigenetic phenomenon that occurs in genetic hybrids and describes the expression of 45S rRNA genes inherited from one progenitor due to the silencing of the other progenitor’s rRNA genes. Nucleolar dominance is a manifestation of rRNA gene dosage control, which also occurs in non-hybrids, regulating the number of active rRNA genes according to the cellular demand for ribosomes and protein synthesis. Ribosomal RNA gene silencing involves changes in DNA methylation an...

  16. Inducible Systemic RNA Silencing in Caenorhabditis elegans

    OpenAIRE

    Timmons, Lisa; Tabara, Hiroaki; Mello, Craig C.; Fire, Andrew Z.

    2003-01-01

    Introduction of double-stranded RNA (dsRNA) can elicit a gene-specific RNA interference response in a variety of organisms and cell types. In many cases, this response has a systemic character in that silencing of gene expression is observed in cells distal from the site of dsRNA delivery. The molecular mechanisms underlying the mobile nature of RNA silencing are unknown. For example, although cellular entry of dsRNA is possible, cellular exit of dsRNA from normal anim...

  17. Active compressor engine silencer reduces exhaust noise

    International Nuclear Information System (INIS)

    An active industrial silencer on a compressor engine at a Tenneco Gas station has reduced low-frequency 'rumbling' noise by 8 dB during trials while lowering backpressure about 90$. This 8 dB reduction of the piston firing frequency corresponds to a more than 80% decrease in emitted acoustic power. The silencing unit, installed on one of six engines at the station near Eden, N.Y., continues in operation. Based on the results, the manufacturer is identifying additional compressor sites for further tests. This paper reviews this project

  18. “The Silence Itself is Enough of a Statement”: Unintended Consequences of Silence as an Awareness-Raising Strategy

    OpenAIRE

    Woolley, Susan W.

    2010-01-01

    The strategy of silence for voice, as seen in the Day of Silence, deploys silence in order to draw attention to the ways in which an individual or group has been silenced and to establish possibilities for voice. The Day of Silence is a nation-wide day of action aimed at addressing anti-LGBTQ bias and harassment in schools. This ethnographic study of a high school gay-straight alliance (GSA) club examines the unintended consequences of silence as an awareness-raising strategy during events ...

  19. Surprised by Bird, Bard, and Bach: Language, Silence, and Transcendence.

    Science.gov (United States)

    Suhor, Charles

    1991-01-01

    Argues the importance of the relationships among silence and literature, the arts, and other experiences that point toward transcendence. Suggests that English teachers can expand the repertoire of classroom activities and teaching techniques that make use of silence. (KEH)

  20. Mainstream Television, Adolescent Homosexuality, and Significant Silence.

    Science.gov (United States)

    Kielwasser, Alfred P.; Wolf, Michelle A.

    1992-01-01

    Argues that the symbolic annihilation of gay and lesbian youth exhibited by network television contributes to a dysfunctional isolation supported by the mutually reinforcing invisibility of homosexual adolescents on television and in the real world. Suggests that the spiral of silence also partially accounts for the inefficacy of oppositional…

  1. Veiled Word(s) – Sacred Silence

    DEFF Research Database (Denmark)

    Isar, Nicoletta

    2014-01-01

    or secret prayer, and divine silence, which are at the very centre of the Byzantine altar. The main focus is to investigate the liminal nature of the Mystery, manifested through concealing-revealing devices, which are thresholds in the liturgical participation of the Byzantine subject. Fear and secrecy...

  2. The Power of Silence in To the Lighthouse

    Institute of Scientific and Technical Information of China (English)

    王艳

    2013-01-01

    Traditionally, silence is regarded as an absence, inaction, emptiness, or inferiority, but it figures in Woolf ’s novels as a presence, power, creativity, and superiority, and infused with a new psychic and narrative life. The present paper will examine Woolf’s expression of silence in her masterpiece To the Lighthouse to reveal the power of silence.

  3. The Differences of Silence between Chinese and American Culture

    Institute of Scientific and Technical Information of China (English)

    巩飞

    2015-01-01

    Language is an important means of human communication; and silence can also convey a wealth of information.This paper will interpret the different definitions of silence phenomena between China and America and two different attitudes and representations of silence.It will help us to improve the effectiveness of communication.

  4. Unpacking the Unspoken: Silence in Collective Memory and Forgetting

    Science.gov (United States)

    Vinitzky-Seroussi, Vered; Teeger, Chana

    2010-01-01

    Collective memory quite naturally brings to mind notions of mnemonic speech and representation. In this article, however, we propose that collective silences be thought of as a rich and promising arena through which to understand how groups deal with their collective pasts. In so doing, we explore two types of silence: overt silence and covert…

  5. An Empirical Study on English Majors’Silence in Class

    Institute of Scientific and Technical Information of China (English)

    Zhao Lingzhi

    2014-01-01

    This paper aims to investigate the causes of English majors' silence in class and whether task-based approach can reduce silence by conducting an empirical study.The results indicates that students' self-esteem,motivation,personality and teachers' authority are the main causes of students' silence in class.

  6. An Empirical Study on English Majors’ Silence in Class

    Institute of Scientific and Technical Information of China (English)

    Zhao; Lingzhi

    2014-01-01

    This paper aims to investigate the causes of English majors’silence in class and whether task-based approach can reduce silence by conducting an empirical study.The results indicates that students’self-esteem,motivation,personality and teachers’authority are the main causes of students’silence in class.

  7. Dissecting RNA silencing in protoplasts uncovers novel effects of viral suppressors on the silencing pathway at the cellular level

    OpenAIRE

    Qi, Yijun; Zhong, Xuehua; Itaya, Asuka; Ding, Biao

    2004-01-01

    Short interfering RNA (siRNA)-mediated RNA silencing plays an important role in cellular defence against viral infection and abnormal gene expression in multiple organisms. Many viruses have evolved silencing suppressors for counter-defence. We have developed an RNA silencing system in the protoplasts of Nicotiana benthamiana to investigate the functions of viral suppressors at the cellular level. We showed that RNA silencing against a green fluorescent protein (GFP) reporter gene in the prot...

  8. Silence:An Effective Resistance in"No Name Woman"

    Institute of Scientific and Technical Information of China (English)

    戴淑琴

    2016-01-01

    "No Name Woman", written by Maxine Hong Kingston, depicts different life of Chinese or Chinese American women. They go through different life experiences, but their life experiences reflect the same attitude toward life that is silence. Is si-lence effective or not? By analyzing the textual contents, life experience of the aunt combining with contemporary social envi-ronment, the paper argues that silence is an effective resistance against patriarchal system. It illuminates the ways that resistance not only relies on violence, but also on silence and sometimes silence is more powerful than violence.

  9. Destructive Role of Employee Silence in Organizational Success

    Directory of Open Access Journals (Sweden)

    Malikeh Beheshtifar

    2012-11-01

    Full Text Available Employees are regarded as major sources of change, creativity, learning, and innovation, which are critical factors to the success of organizations. However, many employees choose not to voice their opinions and concerns about matters in their organizations. Silence can convey approval and sharing or disfavor and opposition, thus becoming a pressure mechanism for both individuals and organizations. Through silence, organizational members suppress concerns about difficult or troubling personal as well as organizational issues. Moreover, there are three types of employee silence as Acquiescent Silence, Defensive Silence, and Pro-social Silence. Fear, embarrassment, narrow conceptions of ethical responsibility, implicated friends, lack of opportunity for voice, and lack of organizational political skills are factors to cause silence. Employee silence has many effects on the employees themselves. Indifferent employees, often products of ignored employee silence, tend to feel like cogs at machinery factories, developing the attitude “to get along, go along”. Indifferent employees cause the organization to lose money and function poorly. If employee silence does occur, communication suffers and as a result harms the overall functioning of the organization. However, it is not easy to break silence climate of employees and their managers. Meanwhile, it is suggested to regulate some rules for supporting the employees' attitudes, to make decisions about the work groups of the organizations and to establish some programs in order to improve the human resource management for training skills of decision – making.

  10. Stability of RNA silencing-based traits after virus infection

    DEFF Research Database (Denmark)

    Jørgensen, Bodil; Albrechtsen, Merete

    2007-01-01

    Induction of post-transcriptional gene silencing (PTGS) by transgenes can be exploited in the genetic engineering of plants for virus resistance, altered lipid or polysaccharide composition, delayed flowering, reduced toxin or allergen content, and many other desired traits. Transformation with...... silencing has raised concerns that virus infection of crop plants might reverse the new silencing-based traits. Most studies of virus suppression of silencing have used model systems based on silencing of reporter genes. A few studies have analysed the effects of virus infections on plants with genetically...... of simple and inverted repeat constructs with respect to resistance stability upon challenge with another virus. We found that silencing induced by an inverted repeat construct persisted after virus infection where silencing induced by a simple sense construct failed. Furthermore, even with a simple...

  11. Structural basis for simvastatin competitive antagonism of complement receptor 3

    DEFF Research Database (Denmark)

    Jensen, Maria Risager; Bajic, Goran; Zhang, Xianwei;

    2016-01-01

    to the complement fragments iC3b and C3d, but not to intercellular adhesion molecule-1. By virtue of the I domain's wide distribution in binding kinetics to ligands, it was possible to identify ligand binding kinetics as discriminator for simvastatin antagonism. In static cellular experiments, 15......The complement system is an important part of the innate immune response to infection, but may also cause severe complications during inflammation. Small molecule antagonists to complement receptor (CR)3 have been widely sought, but a structural basis for their mode of action is not available. We...

  12. Antagonism of Type I Interferon Responses by New World Hantaviruses▿

    OpenAIRE

    Levine, Jessica R.; Prescott, Joseph; Kyle S. Brown; Best, Sonja M.; Ebihara, Hideki; Feldmann, Heinz

    2010-01-01

    Evasion of interferon (IFN)-mediated antiviral signaling is a common defense strategy for pathogenic RNA viruses. To date, research on IFN antagonism by hantaviruses is limited and has focused on only a subset of the numerous recognized hantavirus species. The host IFN response has two phases, an initiation phase, resulting in the induction of alpha/beta IFN (IFN-α/β), and an amplification phase, whereby IFN-α/β signals through the Jak/STAT pathway, resulting in the establishment of the cellu...

  13. Antagonism, social critique and the ‘violent reverie’

    OpenAIRE

    Hook, Derek

    2014-01-01

    This paper opens up a series of windows on racialised life in past and present South Africa as a way arguing for the value of antagonism as a mode of critical enquiry. Sampling a cross-section of recent writing on South African race politics, the paper calls attention both to strident critiques of white privilege, and to concerns over allegedly anti-white populism. Chabani Manganyi’s notion of the violent reverie is used to argue that such oppositional critique affords a crucial expressive mo...

  14. The Marijuana Phenomenon: Contradictions and Silence.

    Science.gov (United States)

    Hall, Joanne M; Shattell, Mona M; McConnell, Elizabeth A

    2016-01-01

    The United States is trending toward more permissiveness regarding recreational and medicinal marijuana (MJ). Many conditions for which MJ is recommended, prescribed, or self-prescribed are symptoms that advanced practice nurses address daily. Yet, the silence of nursing scientists on ethics, practices, and policies regarding such clinical decisions is deafening. This is but one of many contradictions about MJ use that we discuss in this article. We do not propose to resolve these contradictions; that is left to the community of nurse scientists in interprofessional discourse. Collectively, we must explore these contradictions and, through evidence-based policy recommendations, overcome the silence about how providers view MJ, how it might be helpful, its risks, and cultural shifts that have accompanied a changed political/legal environment. Long term, we must close the gaps in the nursing knowledge base regarding MJ as it affects users and how it is used interventionally. PMID:26950836

  15. Silencing FAT10 inhibits metastasis of osteosarcoma.

    Science.gov (United States)

    Ma, Chengbin; Zhang, Zhiyu; Cui, Yan; Yuan, Hongmou; Wang, Feng

    2016-08-01

    Metastasis is the main challenge of osteosarcoma treatment. Herein, we first reveal the oncogenic role of FAT10 in metastasis of osteosarcoma. FAT10 was upregulated in osteosarcoma, especially in metastatic osteosarcoma. High level of FAT10 was associated with poorer prognosis of osteosarcoma patients. Moreover, Transwell and Matrigel assays revealed that silencing FAT10 significantly inhibited the invasive and migratory abilities of osteosarcoma cells. Metastasis assay in vivo showed that silencing FAT10 decreased the number of mice with distant metastasis. We also found that FAT10 may act its oncogenic functions through regulating HOXB9. Collectively, the results suggested that FAT10 may be a novel therapeutic target for osteosarcoma patients. PMID:27279480

  16. Elucidating MOM1-mediated gene silencing

    OpenAIRE

    Smathajitt, Chotika

    2007-01-01

    Chez Arabidopsis, la protéine MOM1 (Morpheus' Molecule 1) est impliquée dans le silencing épigénétique des gènes. La mutante "mom1" ne présente aucun changement de méthylation de l'ADN, de modifications des histones ou de l'architecture nucléaire. Ces caractéristiques différencient nettement MOM1 des autres régulateurs épigénétiques connus. Durant ma thèse, j'ai utilisé deux approches afin d'identifier des composants additionnels participant au silencing dirigé par MOM1. La première approche ...

  17. Silencing Cinema. Film Censorship around the World

    OpenAIRE

    2013-01-01

    Why does oppression by censorship affect the film industry far more frequently than any other mass media? "Silencing Cinema" brings together the key issues and authors to examine instances of film censorship throughout the world. Including essays by some of today's leading film historians, the book offers groundbreaking historical research on film censorship in major film production countries, including the United States, the United Kingdom, Russia/Soviet Union, India, China, and Nigeria, amo...

  18. Underground laboratories: Cosmic silence, loud science

    International Nuclear Information System (INIS)

    Underground laboratories provide the low radioactive background environment necessary to host key experiments in the field of particle and astroparticle physics, nuclear astrophysics and other disciplines that can profit of their characteristics and of their infrastructures. The cosmic silence condition existing in these laboratories allows the search for extremely rare phenomena and the exploration of the highest energy scales that cannot be reached with accelerators. I briefly describe all the facilities that are presently in operation around the world.

  19. Analysis and design of pod silencers

    Science.gov (United States)

    Munjal, M. L.

    2003-05-01

    Parallel baffle mufflers or split silencers are used extensively in heating, ventilation and air conditioning systems for increased attenuation of noise within a short or given length. Acoustic analysis of rectangular parallel baffle mufflers runs on the same lines as that of a rectangular duct lined on two sides. This simplification would not hold for circular configurations. Often, a cylindrical pod is inserted into a circular lined duct to increase its attenuation (or transmission loss), thereby making the flow passage annular and providing an additional absorptive layer on the inner side of this annular passage. This configuration, called a pod silencer, is analyzed here for the four-pole parameters as well as transmission loss, making use of the bulk reaction model. The effect of thin protective film or a highly perforated metallic plate is duly incorporated by means of a grazing-flow impedance. Use of appropriate boundary conditions leads to a set of linear homogeneous equations which in turn lead to a transcendental frequency equation in the unknown complex axial wave number. This is solved by means of the Newton-Raphson method, and the axial wave number is then used in the expressions for transmission loss as well as the transfer matrix parameters. Finally, results of a parametric study are reported to help the designer in optimization of a pod silencer configuration within a given overall size for minimal cost.

  20. Gas turbine exhaust system silencing design

    International Nuclear Information System (INIS)

    Gas turbines are the preferred prime mover in many applications because of their high efficiency, fuel flexibility, and low environmental impact. A typical mid-size machine might have a power rating of 80 MW, a flow of about 1000 kg/hr, and an exhaust temperature of over 500C. The most powerful single source of noise is generally the exhaust, which may generate over a kilowatt of acoustic energy. This paper reports that there are two important ways in which exhaust systems can radiate noise. The first is through the discharge of the exhaust duct, with the exhaust gas. Because of the large quantity of hot gas, the duct exit is always oriented vertically; it may be fairly high in the air in order to promote dispersion of the exhaust plume. This source is almost always attenuated by means of a silencer located somewhere in the ductwork. The second source of noise is often called breakout; it is the radiation of exhaust noise through the walls of the ducting. Breakout is most important for those sections of the exhaust duct which lie upstream of the silencer, where sound levels inside the ducting are highest. Both exhaust duct exit noise and breakout noise can be calculated from the sound power level of the gas turbine exhaust and the sound transmission loss (TL) of the silencer and ducting

  1. Imipenem antagonism of the in vitro activity of piperacillin against Pseudomonas aeruginosa.

    OpenAIRE

    Bertram, M A; Young, L. S.

    1984-01-01

    The MICs of imipenem and piperacillin, alone and in combination, against Pseudomonas aeruginosa were determined in a checkerboard titration microdilution assay. A dramatic, one-way antagonism of imipenem for piperacillin was demonstrated in 28 of the 35 strains examined; antagonism was associated with the induction of a beta-lactamase.

  2. A silencing safeguard: links between RNA silencing and mRNA processing in Arabidopsis

    OpenAIRE

    Chen, Xuemei

    2008-01-01

    RNA silencing is a genome defense mechanism that many eukaryotic organisms use to fight the invasion of viruses and to control transposable elements. Work by Gregory et al. on Arabidopsis thaliana reported in this issue (Gregory et al., 2008) revealed that this mechanism can backfire to silence endogenous protein-coding transcripts unless the plant is vigilant about mRNA quality control. They also uncovered an unexpected role of the cap-binding protein ABH1 (Hugouvieux et al., 2001) in miRNA ...

  3. Analysis of Silences in“The Dumb Waiter”

    Institute of Scientific and Technical Information of China (English)

    张晓莉

    2013-01-01

    Harold Pinter is one of the famous absurdist play writer in England. His works and language are full of absurd color, which is the focus of critics. Silence is a trademark of Harold Pinter’s writing. He uses it to an exquisite manner that he forms his individual“Pinteresque”silence. Silences in his play appear many times and act as a natural barrier for true self. This paper will take Pinter’s early work“The Dumb Waiter”for example to analysis the wide usage of silences in the play. The paper tries to un-mask the truth under silences. And by exploring the two types of silences, we can see characters ’true emotion and intention un-derground.

  4. Organizational Silence in Universities as the Predictor of Organizational Culture

    OpenAIRE

    Erkan YAMAN; Kayhan RUÇLAR

    2014-01-01

    The aim of this study is to determine the relationship between the sense of organizational silence and the organizational culture the instructors perceived. In this study, the scale for determining organizational culture developed by İpek (1999) and the scale for measuring organizational silence developed by Çakıcı (2007) and adapted by Soycan (2010) are used. No remarkable difference was found in the academic staff's sense of organizational silence degree according to their genders and educa...

  5. Novel RNA-based Strategies for Therapeutic Gene Silencing

    OpenAIRE

    Sibley, Christopher R.; Seow, Yiqi; Wood, Matthew JA

    2010-01-01

    The past decade has seen intense scientific interest in non-coding RNAs. In particular, the discovery and subsequent exploitation of gene silencing via RNA interference (RNAi) has revolutionized the way in which gene expression is now studied and understood. It is now well established that post-transcriptional gene silencing (PTGS) by the microRNA (miRNA) and other RNAi-associated pathways represents an essential layer of complexity to gene regulation. Gene silencing using RNAi additionally d...

  6. Aryl hydrocarbon receptor antagonism and its role in rheumatoid arthritis

    Science.gov (United States)

    Nguyen, Nam Trung; Nakahama, Taisuke; Nguyen, Chi Hung; Tran, Trang Thu; Le, Van Son; Chu, Hoang Ha; Kishimoto, Tadamitsu

    2015-01-01

    Although rheumatoid arthritis (RA) is the most common autoimmune disease, affecting approximately 1% of the population worldwide, its pathogenic mechanisms are poorly understood. Tobacco smoke, an environmental risk factor for RA, contains several ligands of aryl hydrocarbon receptor (Ahr), also known as dioxin receptor. Ahr plays critical roles in the immune system. We previously demonstrated that Ahr in helper T-cells contributes to development of collagen-induced arthritis, a mouse model of RA. Other studies have shown that cigarette smoke condensate and pure Ahr ligands exacerbate RA by altering bone metabolism and inducing proinflammatory responses in fibroblast-like synoviocytes. Consistent with these findings, several Ahr antagonists such as α-naphthoflavone, resveratrol, and GNF351 reverse the effect of Ahr ligands in RA pathogenesis. In this review, we summarize the current knowledge of Ahr function in the immune system and the potential clinical benefits of Ahr antagonism in treating RA.

  7. Interferon Induction by RNA Viruses and Antagonism by Viral Pathogens

    Directory of Open Access Journals (Sweden)

    Yuchen Nan

    2014-12-01

    Full Text Available Interferons are a group of small proteins that play key roles in host antiviral innate immunity. Their induction mainly relies on host pattern recognition receptors (PRR. Host PRR for RNA viruses include Toll-like receptors (TLR and retinoic acid-inducible gene I (RIG-I like receptors (RLR. Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens. Because of the important roles of interferons, viruses have evolved multiple strategies to evade host TLR and RLR mediated signaling. This review focuses on the mechanisms of interferon induction and antagonism of the antiviral strategy by RNA viruses.

  8. The Enamovirus P0 protein is a silencing suppressor which inhibits local and systemic RNA silencing through AGO1 degradation.

    Science.gov (United States)

    Fusaro, Adriana F; Correa, Regis L; Nakasugi, Kenlee; Jackson, Craig; Kawchuk, Lawrence; Vaslin, Maite F S; Waterhouse, Peter M

    2012-05-10

    The P0 protein of poleroviruses and P1 protein of sobemoviruses suppress the plant's RNA silencing machinery. Here we identified a silencing suppressor protein (SSP), P0(PE), in the Enamovirus Pea enation mosaic virus-1 (PEMV-1) and showed that it and the P0s of poleroviruses Potato leaf roll virus and Cereal yellow dwarf virus have strong local and systemic SSP activity, while the P1 of Sobemovirus Southern bean mosaic virus supresses systemic silencing. The nuclear localized P0(PE) has no discernable sequence conservation with known SSPs, but proved to be a strong suppressor of local silencing and a moderate suppressor of systemic silencing. Like the P0s from poleroviruses, P0(PE) destabilizes AGO1 and this action is mediated by an F-box-like domain. Therefore, despite the lack of any sequence similarity, the poleroviral and enamoviral SSPs have a conserved mode of action upon the RNA silencing machinery. PMID:22361475

  9. The Enamovirus P0 protein is a silencing suppressor which inhibits local and systemic RNA silencing through AGO1 degradation

    International Nuclear Information System (INIS)

    The P0 protein of poleroviruses and P1 protein of sobemoviruses suppress the plant's RNA silencing machinery. Here we identified a silencing suppressor protein (SSP), P0PE, in the Enamovirus Pea enation mosaic virus-1 (PEMV-1) and showed that it and the P0s of poleroviruses Potato leaf roll virus and Cereal yellow dwarf virus have strong local and systemic SSP activity, while the P1 of Sobemovirus Southern bean mosaic virus supresses systemic silencing. The nuclear localized P0PE has no discernable sequence conservation with known SSPs, but proved to be a strong suppressor of local silencing and a moderate suppressor of systemic silencing. Like the P0s from poleroviruses, P0PE destabilizes AGO1 and this action is mediated by an F-box-like domain. Therefore, despite the lack of any sequence similarity, the poleroviral and enamoviral SSPs have a conserved mode of action upon the RNA silencing machinery.

  10. Development of a reactive silencer for turbocompressors

    OpenAIRE

    González Díez, N.; Smeulers, J.P.M.; Meulendijks, D; König, S.

    2013-01-01

    Turbo compressors can generate tonal noise in a frequency range of 1000 to 5000 Hz, which may cause nuisance in the environment where the machine is installed. The cause of this tonal noise is the interaction between the flow and the rotating blades inside the compressor. The noise is transmitted from the compressor into the pipe system at both suction and discharge sides. Then it is radiated from the pipe walls to the environment. As this noise source can’t be avoided, if necessary a silence...

  11. Heteronormativity and Silenced Sexualities at Work

    OpenAIRE

    Jolanta Reingardė

    2010-01-01

    The paper focuses on workplace as a space in which the normative versions of heterosexuality are produced. Facing the everyday reality of the closet, the majority of homosexual employees constructs and negotiates their silenced sexualities at work. The study is based on 30 in-depth interviews with Lithuanian gays and lesbians carried out within the framework of the EQUAL project “Open and Safe at Work.” The paper discusses how homosexuals confront heteronormativity at work and how it shapes t...

  12. A Modular Plasmid Assembly Kit for Multigene Expression, Gene Silencing and Silencing Rescue in Plants

    Science.gov (United States)

    Binder, Andreas; Lambert, Jayne; Morbitzer, Robert; Popp, Claudia; Ott, Thomas; Lahaye, Thomas; Parniske, Martin

    2014-01-01

    The Golden Gate (GG) modular assembly approach offers a standardized, inexpensive and reliable way to ligate multiple DNA fragments in a pre-defined order in a single-tube reaction. We developed a GG based toolkit for the flexible construction of binary plasmids for transgene expression in plants. Starting from a common set of modules, such as promoters, protein tags and transcribed regions of interest, synthetic genes are assembled, which can be further combined to multigene constructs. As an example, we created T-DNA constructs encoding multiple fluorescent proteins targeted to distinct cellular compartments (nucleus, cytosol, plastids) and demonstrated simultaneous expression of all genes in Nicotiana benthamiana, Lotus japonicus and Arabidopsis thaliana. We assembled an RNA interference (RNAi) module for the construction of intron-spliced hairpin RNA constructs and demonstrated silencing of GFP in N. benthamiana. By combination of the silencing construct together with a codon adapted rescue construct into one vector, our system facilitates genetic complementation and thus confirmation of the causative gene responsible for a given RNAi phenotype. As proof of principle, we silenced a destabilized GFP gene (dGFP) and restored GFP fluorescence by expression of a recoded version of dGFP, which was not targeted by the silencing construct. PMID:24551083

  13. A modular plasmid assembly kit for multigene expression, gene silencing and silencing rescue in plants.

    Directory of Open Access Journals (Sweden)

    Andreas Binder

    Full Text Available The Golden Gate (GG modular assembly approach offers a standardized, inexpensive and reliable way to ligate multiple DNA fragments in a pre-defined order in a single-tube reaction. We developed a GG based toolkit for the flexible construction of binary plasmids for transgene expression in plants. Starting from a common set of modules, such as promoters, protein tags and transcribed regions of interest, synthetic genes are assembled, which can be further combined to multigene constructs. As an example, we created T-DNA constructs encoding multiple fluorescent proteins targeted to distinct cellular compartments (nucleus, cytosol, plastids and demonstrated simultaneous expression of all genes in Nicotiana benthamiana, Lotus japonicus and Arabidopsis thaliana. We assembled an RNA interference (RNAi module for the construction of intron-spliced hairpin RNA constructs and demonstrated silencing of GFP in N. benthamiana. By combination of the silencing construct together with a codon adapted rescue construct into one vector, our system facilitates genetic complementation and thus confirmation of the causative gene responsible for a given RNAi phenotype. As proof of principle, we silenced a destabilized GFP gene (dGFP and restored GFP fluorescence by expression of a recoded version of dGFP, which was not targeted by the silencing construct.

  14. Organizational Silence in Universities as the Predictor of Organizational Culture

    Directory of Open Access Journals (Sweden)

    Erkan YAMAN

    2014-04-01

    Full Text Available The aim of this study is to determine the relationship between the sense of organizational silence and the organizational culture the instructors perceived. In this study, the scale for determining organizational culture developed by İpek (1999 and the scale for measuring organizational silence developed by Çakıcı (2007 and adapted by Soycan (2010 are used. No remarkable difference was found in the academic staff's sense of organizational silence degree according to their genders and educational backgrounds. It was seen that the instructors' sense of organizational silence had remarkable differences according to their age group, faculty, sense of administration type in their institutions, frequency of their face-to-face communication with their administrators and their thoughts of speaking clearly with their administrators. It was observed that research assistants had a significantly higher sense of organizational silence than the lecturers in the sense of ‘Lack of Experience'. It was seen that academicians who had 1-5 years of employment period had the highest sense of organizational silence while those who had 21 years or more employment period had the lowest sense of organizational silence in the sense of ‘Lack of Experience' of organizational silence. When the points that participant academicians got from organizational silence and organizational culture scales analyzed in the correlation table, it was found out that there was a remarkable relationship between the academicians' sense of organizational silence and sense of organizational culture. This relationship was a medium-level negative relationship between subdimensions of two scales. A medium-level negative relationship between the organizational silence (total and the organizational culture was also seen. Based on the findings, university administrators were proposed to create a participant culture in their institutions as well as to encourage instructors to speak clearly and

  15. Multiple suppressors of RNA silencing encoded by both genomic RNAs of the crinivirus, Tomato chlorosis virus

    OpenAIRE

    Cañizares, Mª Carmen; J. Navas-Castillo; Moriones, E

    2008-01-01

    Viruses express proteins with silencing suppression activity to counteract the RNA silencing-mediated defense response of the host. In the family Closteroviridae, examples of multiple-component RNA silencing suppression systems have been reported

  16. Multiple Interpretations of EFL Learners’ Silence in the Iranian Context

    Directory of Open Access Journals (Sweden)

    Reza Ghaffar Samar

    2013-11-01

    Full Text Available Attention to silence as part of the communicative discourse was first drawn in Sack’s (1974 paper, in which it was perceived as a linguistic and communicative form, and from the functional point of view as capable of expressing ideational, interpersonal, and textual functions. Awareness of multiple functions of silence including the referential, emotive, conative, phatic, poetic and metalanguage is of greater significance when it comes to language learning settings, where learners from a different cultural background from the target language are present to learn that language.  In such contexts, awareness of various functions of silence and correct interpretation of it is essential in teacher-student rapport. This paper aims to, first, provide an introduction to the multiple functions of silence in general and then to investigate these functions in EFL classes of Iran’s private language institutes. The researchers’ own teaching experience along with class observations and 2 phases of interview with teachers of those classes comprise the research data. Findings were indicative of teachers’ lack of awareness of diverse communicative functions of silence in class and that this awareness could be raised through the informal interview phases. This paper attests to the fact that not all learner’s silence should be interpreted negatively as lack of attention or knowledge. Teachers need to be aware of the salient meanings of silence in their EFL class and take an appropriate reactive step accordingly.Keywords: silence, Jakobson’s communicative model, culture, EFL, Iran

  17. Optimisation of acoustic silencer for the screw compressor system

    NARCIS (Netherlands)

    Swamy, M.; Lier, L.J. van; Smeulers, J.P.M.

    2014-01-01

    In one of the screw compressor system, designed silencer was not optimal. A great challenge was the large variation in operating conditions, especially the variation of the molecular weight of the gas. There was need to optimize the silencer. This paper describes the acoustic modelling tools to opti

  18. No-Big-Silence teeb klubituuri / Urmas Hännile

    Index Scriptorium Estoniae

    Hännile, Urmas

    2009-01-01

    Rockansamblist No-Big-Silence ja dark-popansamblist Sinine, nende kontsertttuurist mööda Eestimaad, tutvustamisel bändide uued albumid (No-Big-Silence "Starstealer" ja Sinine "Butterflies"), Pärnus on kontsert 24. oktoobril klubis Sugar

  19. An Analysis of Heathcliff’s Silence in Wuthering Heights

    Institute of Scientific and Technical Information of China (English)

    潘琛

    2013-01-01

    Heathcliff is a highly controversial character in Emily Brontë’s canon Wuthering Heights. He is depicted as an incredi-ble conglomeration of enigmas and simplicity, aloofness and affinity, ferocity and vulnerability, inhumanity and heroicity, a man who appears more silent and preoccupied than talkative and carefree, inaudible and incalculable in both words and thoughts. The author of this paper considers that there is much left to be read and contemplate on in Heathcliff ’s silence and thus make a tempa-tive research into Heathcliff’s silence by discerning its manifestations and probing its causes, in order to resonate with the inner touch of this complicated soul and relate his silence with the spirit that Emily Brontë wished to deliver through Wuthering Heights. Heathcliff’s silence manifests as muteness, elusion and colloquial or physical violence. In his whole life, Heathcliff inter-mittently experiences the self-chosen silence and the forced silence. He chooses to be silence out of self-protection and the infe-riority complex;he considers silence as a token of masculinity. And the ruthless force from outside also compels him into a periph-eralized situation where he has to keep silent and struggles against the torture and torment alone.

  20. Reflections on the Silencing the Self Scale and Its Origins

    Science.gov (United States)

    Jack, Dana Crowley

    2011-01-01

    In this article, the author reflects on the Silencing the Self Scale (STSS) and blends her personal and professional thoughts about self-silencing, gender, and depression. For her, the despair of depression deeply involves questions of value and meaning, culture and freedom. The STSS grew from listening to depressed women's voices. From them, the…

  1. Silence in the Second Language Classrooms of Japanese Universities

    Science.gov (United States)

    King, Jim

    2013-01-01

    Japanese language learners' proclivity for silence has been alluded to by various writers (e.g. Anderson 1993; Korst 1997; Greer 2000) and is supported by plenty of anecdotal evidence, but large-scale, empirical studies aimed at measuring the extent of macro-level silence within Japanese university L2 classrooms are notably lacking. This article…

  2. Strategies underlying RNA silencing suppression by negative strand RNA viruses

    NARCIS (Netherlands)

    Hemmes, J.C.

    2007-01-01

    The research described in this thesis focused on the strategies of negative strand RNA viruses to counteract antiviral RNA silencing. In plants and insects, RNA silencing has been shown to act as a sequence specific antiviral defence mechanism that is characterised by the processing of double strand

  3. Small RNA binding is a common strategy to suppress RNA silencing by several viral suppressors

    OpenAIRE

    Lakatos, Lóránt; Csorba, Tibor; Pantaleo, Vitantonio; Chapman, Elisabeth J.; Carrington, James C.; LIU, Yu-Ping; Dolja, Valerian V.; Calvino, Lourdes Fernández; López-Moya, Juan José; Burgyán, József

    2006-01-01

    RNA silencing is an evolutionarily conserved system that functions as an antiviral mechanism in higher plants and insects. To counteract RNA silencing, viruses express silencing suppressors that interfere with both siRNA- and microRNA-guided silencing pathways. We used comparative in vitro and in vivo approaches to analyse the molecular mechanism of suppression by three well-studied silencing suppressors. We found that silencing suppressors p19, p21 and HC-Pro each inhibit the intermediate st...

  4. Chinanteco children’s silences in different classroom situations

    Directory of Open Access Journals (Sweden)

    Valeria Rebolledo Angulo

    2016-01-01

    Full Text Available This article analyzes, from an ethnographic perspective and a sociocultural framework, the construction of silences in the interaction between students and teachers in a multilingual classroom situation in an indigenous community in méxico. the analysis reveals how the silence of the chinanteco speaking children when asked to answer certain questions in class is not always due to their failure to understand spoken and written spanish that is used in class. their silences are responses taking different meanings in specific situations. the silence of the children can be a way of resisting, a way of hiding, and, sometimes, their voices are silenced.

  5. Cooperation, Trust, and Antagonism: How Public Goods Are Promoted.

    Science.gov (United States)

    Parks, Craig D; Joireman, Jeff; Van Lange, Paul A M

    2013-12-01

    One of the most continually vexing problems in society is the variability with which citizens support endeavors that are designed to help a great number of people. In this article, we examine the twin roles of cooperative and antagonistic behavior in this variability. We find that each plays an important role, though their contributions are, understandably, at odds. It is this opposition that produces seeming unpredictability in citizen response to collective need. In fact, we suggest that careful consideration of the research allows one to often predict when efforts to provide a collectively beneficial good will succeed and when they will fail. To understand the dynamics of participation in response to collective need, it is necessary to distinguish between the primary types of need situations. A public good is an entity that relies in whole or in part on contributions to be provided. Examples of public goods are charities and public broadcasting. Public goods require that citizens experience a short-term loss (of their contribution) in order to realize a long-term gain (of the good). However, because everyone can use the good once it is provided, there is also an incentive to not contribute, let others give, and then take advantage of their efforts. This state of affairs introduces a conflict between doing what is best for oneself and what is best for the group. In a public goods situation, cooperation and antagonism impact how one resolves this conflict. The other major type of need situation is a common-pool resource problem. Here, a good is fully provided at the outset, and citizens may sample from it. The resource is usually, but not necessarily, partially replenished. Examples of replenished resources are drinking water and trees; examples of resources that are functionally not replenished are oil and minerals. Common-pool resources allow citizens to experience a short-term gain (by getting what they want in the early life of the resource) but also present

  6. Antisense Gene Silencing: Therapy for Neurodegenerative Disorders?

    Directory of Open Access Journals (Sweden)

    Troels T. Nielsen

    2013-09-01

    Full Text Available Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how the technique is exploited in a pre-clinical and clinical perspective in relation to neurodegenerative disorders.

  7. SYNERGISM AND ANTAGONISM IN MODEL SYSTEM OF OXIDATION OF SULFUR-CONTAINING WASTEWATERS

    OpenAIRE

    Sivtseva, Anastasia; Zhilenko, Marina; Sivtsev, Vasiliy

    2014-01-01

    The joint oxidation of cysteine and sodium sulfide by molecular oxygen is investigated. Identified the mutual influence of these processes in strongly alkaline media in the presence and in the absence of a catalyst, which causes the occurrence of synergism and antagonism in the system. The causes of these effects can be: sequential course of oxidation of sodium sulfide and cysteine in a mix solutions to show negative effects (antagonism). Positive effect (synergism) due to the influence of th...

  8. Progress in Researches on the Effect of Acupuncture in Antagonizing Oxygen Stress

    Institute of Scientific and Technical Information of China (English)

    LI Zhong-ren; SHEN Mei-hong; PENG Yong-jun

    2005-01-01

    Oxidation and free radicals participate in the pathological process of multiple diseases in organisms, and acupuncture shows good effect in antagonizing oxygen stress (OS). This article reviews the effect of acupuncture in antagonizing oxygen stress and the mechanism of its antifree radical effect in various diseases. The authors hold that acupuncture not only has a chain-blocking effect, but also has preventive and repairing effects of anti-oxidation. And anti-OS action is one of the important mechanisms of acupuncture.

  9. Tachykinin receptors antagonism for asthma: a systematic review

    Directory of Open Access Journals (Sweden)

    Couto Nuno

    2011-08-01

    Full Text Available Abstract Background Tachykinins substance P, neurokinin A and neurokinin B seem to account for asthma pathophysiology by mediating neurogenic inflammation and several aspects of lung mechanics. These neuropeptides act mainly by their receptors NK1, NK2 and NK3, respectively which may be targets for new asthma therapy. Methods This review systematically examines randomized controlled trials evaluating the effect of tachykinins receptors antagonism on asthma. Symptoms, airway inflammation, lung function and airway inflammation were considered as outcomes. We searched the Cochrane Airways Group Specialized Register of Asthma Trials, Cochrane Database of Systematic Reviews, MEDLINE/PubMed and EMBASE. The search is as current as June 2010. Quality rating of included studies followed the Cochrane Collaboration and GRADE Profiler approaches. However, data were not pooled together due to different measures among the studies. Results Our systematic review showed the potential of NK receptor antagonist to decrease airway responsiveness and to improve lung function. However, effects on airway inflammation and asthma symptoms were poorly or not described. Conclusion The limited available evidence suggests that tachykinin receptors antagonists may decrease airway responsiveness and improve lung function in patients with asthma. Further large randomized trials are still required.

  10. Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism.

    Science.gov (United States)

    Vande Burgt, Nathan H; Kaletsky, Rachel L; Bates, Paul

    2015-10-01

    Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP), to counteract restriction and promote virus release. Unlike other tetherin antagonists such as HIV-1 Vpu or KSHV K5, the features within EboGP needed to overcome tetherin are not well characterized. Here, we describe sequences within the EboGP ectodomain and membrane spanning domain (msd) as necessary to relieve tetherin restriction of viral particle budding. Fusing the EboGP msd to a normally secreted form of the glycoprotein effectively promotes Ebola virus particle release. Cellular protein or lipid anchors could not substitute for the EboGP msd. The requirement for the EboGP msd was not specific for filovirus budding, as similar results were seen with HIV particles. Furthermore trafficking of chimeric proteins to budding sites did not correlate with an ability to counter tetherin. Additionally, we find that a glycoprotein construct, which mimics the cathepsin-activated species by proteolytic removal of the EboGP glycan cap and mucin domains, is unable to counteract tetherin. Combining these results suggests an important role for the EboGP glycan cap and msd in tetherin antagonism. PMID:26516900

  11. Antagonism by theophylline of respiratory inhibition induced by adenosine.

    Science.gov (United States)

    Eldridge, F L; Millhorn, D E; Kiley, J P

    1985-11-01

    The effects on respiration of an analogue of adenosine, L-2-N6-(phenylisopropyl)adenosine (PIA), and of the methylxanthine, theophylline, were determined in 19 vagotomized glomectomized cats whose end-tidal PCO2 was kept constant by means of a servo-controlled ventilator. Integrated phrenic nerve activity was used to represent respiratory output. Our results show that PIA, whether given systemically or into the third cerebral ventricle, depressed respiration. Systemically administered theophylline stimulated respiration. Theophylline given intravenously, or into the third ventricle not only reversed the depressive effects of previously administered PIA but caused further increases of respiration above the control level. Prior systemic administration of theophylline blocked both respiratory and hypotensive effects of subsequently administered PIA. Effects of either agent on medullary extracellular fluid pH did not explain the results. We conclude that the adenosine analogue PIA, acts to inhibit neurons in the brain that are involved in the control of respiration and that its effects are blocked by theophylline. We suggest that adenosine acts as a tonic modulator of respiration and that theophylline stimulates breathing by competitive antagonism of adenosine at neuronal receptor sites. PMID:4066573

  12. Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis

    Directory of Open Access Journals (Sweden)

    Zhang Junjie

    2011-02-01

    Full Text Available Abstract Background Autotaxin (ATX is a secreted glycoprotein with the lysophospholipase D (lysoPLD activity to convert lysophosphatidylcholine (LPC into lysophosphatidic acid (LPA, a bioactive lysophospholipid involved in diverse biological actions. ATX is highly expressed in some cancer cells and contributes to their tumorigenesis, invasion, and metastases, while in other cancer cells ATX is silenced or expressed at low level. The mechanism of ATX expression regulation in cancer cells remains largely unknown. Results In the present study, we demonstrated that trichostatin A (TSA, a well-known HDAC inhibitor (HDACi, significantly induced ATX expression in SW480 and several other cancer cells with low or undetectable endogenous ATX expression. ATX induction could be observed when HDAC3 and HDAC7 were down-regulated by their siRNAs. It was found that HDAC7 expression levels were low in the cancer cells with high endogenous ATX expression. Exogenous over-expression of HDAC7 inhibited ATX expression in these cells in a HDAC3-dependent manner. These data indicate that HDAC3 and HDAC7 collaboratively suppress ATX expression in cancer cells, and suggest that TSA induce ATX expression by inhibiting HDAC3 and HDAC7. The biological significance of this regulation mechanism was revealed by demonstrating that TSA-induced ATX protected cancer cells against TSA-induced apoptosis by producing LPA through its lysoPLD activity, which could be reversed by BrP-LPA and S32826, the inhibitors of the ATX-LPA axis. Conclusions We have demonstrated that ATX expression is repressed by HDAC3 and HDAC7 in cancer cells. During TSA treatment, ATX is induced due to the HDAC3 and HDAC7 inhibition and functionally antagonizes the TSA-induced apoptosis. These results reveal an internal HDACi-resistant mechanism in cancer cells, and suggest that the inhibition of ATX-LPA axis would be helpful to improve the efficacy of HDACi-based therapeutics against cancer.

  13. Suppressors of RNA silencing encoded by tomato leaf curl betasatellites

    Indian Academy of Sciences (India)

    Richa Shukla; Sunita Dalal; V G Malathi

    2013-03-01

    Virus encoded RNA-silencing suppressors (RSSs) are the key components evolved by the viruses to counter RNA-silencing defense of plants. Whitefly-transmitted begomoviruses infecting tomato crop code for five different proteins, ORF AC4, ORF AC2 and ORF AV2 in DNA-A component, ORF BV1 in DNA-B and ORF C1 in satellite DNA which are predicted to function as silencing suppressors. In the present study suppressor function of ORF C1 of three betasatellites Tomato leaf curl Bangalore betasatellite ToLCBB-[IN:Hess:08], Cotton leaf curl Multan betasatellite CLCuMB–[IN:Sri:02] and Luffa leaf distortion betasatellite LuLDB-[IN:Lu:04] were examined. Agroinfiltration of GFP-silenced Nicotiana tabaccum cv. Xanthi with the cells expressing C1 protein resulted in reversal of silenced GFP expression. GFP-siRNA level was more than 50-fold lower compared to silenced plants in plants infiltrated with C1 gene from ToLCBB. However, in the case of 35S-C1 CLCuMB and 35S-C1 LuLDB construct, although GFP was expressed, siRNA level was not reduced, indicating that the step at which C1 interfere in RNA-silencing pathway is different.

  14. The effect of eccentricity and spatiotemporal energy on motion silencing.

    Science.gov (United States)

    Choi, Lark Kwon; Bovik, Alan C; Cormack, Lawrence K

    2016-03-01

    The now well-known motion-silencing illusion has shown that salient changes among a group of objects' luminances, colors, shapes, or sizes may appear to cease when objects move rapidly (Suchow & Alvarez, 2011). It has been proposed that silencing derives from dot spacing that causes crowding, coherent changes in object color or size, and flicker frequencies combined with dot spacing (Choi, Bovik, & Cormack, 2014; Peirce, 2013; Turi & Burr, 2013). Motion silencing is a peripheral effect that does not occur near the point of fixation. To better understand the effect of eccentricity on motion silencing, we measured the amount of motion silencing as a function of eccentricity in human observers using traditional psychophysics. Fifteen observers reported whether dots in any of four concentric rings changed in luminance over a series of rotational velocities. The results in the human experiments showed that the threshold velocity for motion silencing almost linearly decreases as a function of log eccentricity. Further, we modeled the response of a population of simulated V1 neurons to our stimuli. We found strong matches between the threshold velocities on motion silencing observed in the human experiment and those seen in the energy model of Adelson and Bergen (1985). We suggest the plausible explanation that as eccentricity increases, the combined motion-flicker signal falls outside the narrow spatiotemporal frequency response regions of the modeled receptive fields, thereby reducing flicker visibility. PMID:27019052

  15. Mechanistic understanding of MeHg-Se antagonism in soil-rice systems: the key role of antagonism in soil

    Science.gov (United States)

    Wang, Yongjie; Dang, Fei; Evans, R. Douglas; Zhong, Huan; Zhao, Jiating; Zhou, Dongmei

    2016-01-01

    Methylmercury (MeHg) accumulation in rice has great implications for human health. Here, effects of selenium (Se) on MeHg availability to rice are explored by growing rice under soil or foliar fertilization with Se. Results indicate that soil amendment with Se could reduce MeHg levels in soil and grain (maximally 73%). In contrast, foliar fertilization with Se enhanced plant Se levels (3-12 folds) without affecting grain MeHg concentrations. This evidence, along with the distinct distribution of MeHg and Se within the plant, demonstrate for the first time that Se-induced reduction in soil MeHg levels (i.e., MeHg-Se antagonism in soil) rather than MeHg-Se interactions within the plant might be the key process triggering the decreased grain MeHg levels under Se amendment. The reduction in soil MeHg concentrations could be mainly attributed to the formation of Hg-Se complexes (detected by TEM-EDX and XANES) and thus reduced microbial MeHg production. Moreover, selenite and selenate were equally effective in reducing soil MeHg concentrations, possibly because of rapid changes in Se speciation. The dominant role of Se-induced reduction in soil MeHg levels, which has been largely underestimated previously, together with the possible mechanisms advance our mechanistic understanding about MeHg dynamics in soil-rice systems.

  16. Strategies underlying RNA silencing suppression by negative strand RNA viruses

    OpenAIRE

    Hemmes, J.C.

    2007-01-01

    The research described in this thesis focused on the strategies of negative strand RNA viruses to counteract antiviral RNA silencing. In plants and insects, RNA silencing has been shown to act as a sequence specific antiviral defence mechanism that is characterised by the processing of double stranded (ds)RNA ‘trigger’ molecules into small interfering RNAs (siRNAs) by enzymes of the Dicer family. The siRNA molecules are essential components of the RNA induced silencing complex (RISC), which u...

  17. Two classes of short interfering RNA in RNA silencing

    OpenAIRE

    Hamilton, Andrew; Voinnet, Olivier; Chappell, Louise; Baulcombe, David

    2015-01-01

    RNA silencing is a eukaryotic genome defence system that involves processing of double-stranded RNA (dsRNA) into 21–26 nt, short interfering RNA (siRNA). The siRNA mediates suppression of genes corresponding to the dsRNA through targeted RNA degradation. In some plant systems there are additional silencing processes, involving systemic spread of silencing and RNA-directed methylation/transcriptional suppression of homologous genomic DNA. We show here that siRNAs produced in plants from a gree...

  18. Transcriptional silencing of multiple genes in trophozoites of Entamoeba histolytica.

    Directory of Open Access Journals (Sweden)

    Rivka Bracha

    2006-05-01

    Full Text Available In a previous work we described the transcriptional silencing of the amoebapore A (AP-A gene (Ehap-a of Entamoeba histolytica strain HM-1:IMSS. The silencing occurred following transfection with a plasmid containing a 5' upstream region (473 bp of Ehap-a that included a truncated segment (140 bp of a short interspersed nuclear element (SINE1. Silencing remained in effect even after removal of the plasmid (clone G3. Neither short interfering RNA nor methylated DNA were detected, but the chromatin domain of Ehap-a in the gene-silenced trophozoites was modified. Two other similar genes (Ehap-b and one encoding a Saposin-like protein, SAPLIP 1 also became silenced. In the present work we demonstrate the silencing of a second gene of choice, one that encodes the light subunit of the Gal/GalNAc inhibitable lectin (Ehlgl1 and the other, the cysteine proteinase 5 (EhCP-5. This silencing occurred in G3 trophozoites transfected with a plasmid in which the 473 bp 5' upstream Ehap-a fragment was directly ligated to the second gene. Transcriptional silencing occurred in both the transgene and the chromosomal gene. SINE1 sequences were essential, as was a direct connection between the Ehap-a upstream region and the beginning of the open reading frame of the second gene. Gene silencing did not occur in strain HM-1:IMSS with any of these plasmid constructs. The trophozoites with two silenced genes were virulence-attenuated as were those of clone G3. In addition, trophozoites not expressing Lgl1 and AP-A proteins had a significantly reduced ability to cap the Gal/GalNAc-lectin to the uroid region when incubated with antibodies against the heavy (170 kDa subunit of the lectin. Lysates of trophozoites lacking cysteine proteinase 5 and AP-A proteins had 30% less cysteine proteinase activity than those of HM-1:IMSS strain or the G3 clone. Silencing of other genes in G3 amoebae could provide a model to study their various functions. In addition, double gene-silenced

  19. Epigenetic history of an Arabidopsis trans-silencer locus and a test for relay of trans-silencing activity

    Directory of Open Access Journals (Sweden)

    von Arnim Albrecht G

    2002-12-01

    Full Text Available Abstract Background Meiotically heritable epimutations affecting transgene expression are not well understood, even and in particular in the plant model species, Arabidopsis thaliana. The Arabidopsis trans-silencer locus, C73, which encodes a fusion protein between the repressor of photomorphogenesis, COP1, and green fluorescent protein (GFP-COP1, heritably modifies the expression pattern and cop1-like cosuppression phenotypes of multiple GFP-COP1 target loci by transcriptional gene silencing. Results Here we describe three additional features of trans-silencing by the C73 locus. First, the silencing phenotype of C73 and of similar complex loci was acquired epigenetically over the course of no more than two plant generations via a stage resembling posttranscriptional silencing. Second, imprints imposed by the C73 locus were maintained heritably for at least five generations in the absence of the silencer with only sporadic spontaneous reversion. Third, the pairing of two other GFP-COP1 transgene loci, L91 and E82, showed an increased tendency for epigenetic modification when L91 carried an epigenetic imprint from C73, but not when E82 bore the imprint. Conclusions The latter data suggest a transfer of trans-silencing activity from one transgene locus, C73, to another, namely L91. These results extend our operational understanding of interactions among transgenes in Arabidopsis.

  20. Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

    Science.gov (United States)

    Kroon, Jan; Puhr, Martin; Buijs, Jeroen T; van der Horst, Geertje; Hemmer, Daniëlle M; Marijt, Koen A; Hwang, Ming S; Masood, Motasim; Grimm, Stefan; Storm, Gert; Metselaar, Josbert M; Meijer, Onno C; Culig, Zoran; van der Pluijm, Gabri

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance. In this study, we aim to elucidate the role of the GR in docetaxel-resistant PCa in order to improve the current PCa therapies. GR expression was analyzed in a tissue microarray of primary PCa specimens from chemonaive and docetaxel-treated patients, and in cultured PCa cell lines with an acquired docetaxel resistance (PC3-DR, DU145-DR, and 22Rv1-DR). We found a robust overexpression of the GR in primary PCa from docetaxel-treated patients and enhanced GR levels in cultured docetaxel-resistant human PCa cells, indicating a key role of the GR in docetaxel resistance. The capability of the GR antagonists (RU-486 and cyproterone acetate) to revert docetaxel resistance was investigated and revealed significant resensitization of docetaxel-resistant PCa cells for docetaxel treatment in a dose- and time-dependent manner, in which a complete restoration of docetaxel sensitivity was achieved in both androgen receptor (AR)-negative and AR-positive cell lines. Mechanistically, we demonstrated down-regulation of Bcl-xL and Bcl-2 upon GR antagonism, thereby defining potential treatment targets. In conclusion, we describe the involvement of the GR in the acquisition of docetaxel resistance in human PCa. Therapeutic targeting of the GR effectively resensitizes docetaxel-resistant PCa cells. These findings warrant further investigation of the clinical utility of the GR antagonists in the management of patients with advanced and docetaxel-resistant PCa. PMID:26483423

  1. Viral counterdefense on RNA silencing : analysis of RNA silencing suppressors from arthropod-borne negative strand RNA plant viruses

    OpenAIRE

    Schnettler, E.

    2010-01-01

    This thesis describes that RNA silencing suppressor (RSS) proteins encoded by negative-stranded RNA plant viruses are able to interfere with different RNA silencing pathways in a variety of organisms by interacting with double stranded (ds)RNA molecules. These RSS proteins are able to counteract the antiviral RNA silencing response in their plant host and insect vector, and even in mammalian cells, that are non-hosts for these viruses. Whereas Rice hoja blanca virus NS3 has been shown to bind...

  2. Implications of Silence in Conversation within the Framework of Cooperative Principle

    Institute of Scientific and Technical Information of China (English)

    Chen Shiyao

    2014-01-01

    Silence is a common linguistic phenomenon which plays an important role in communication. This paper, taking a pragmatic perspective, analyzes silence in human communication and points out its pragmatic value. It indicates that silence is not a negative phenomenon with the Cooperative Principle and then deals with the implications of silence in conversation.

  3. Nuclear RNA silencing and related phenomena in animals

    Czech Academy of Sciences Publication Activity Database

    Malík, Radek; Svoboda, Petr

    Chichester: Wiley, 2012 - (Sahu, S.), s. 297-315 ISBN 9781119976097 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : nuclear RNA silencing * small RNAs * Dicer Subject RIV: EB - Genetics ; Molecular Biology

  4. Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity

    OpenAIRE

    Wilkemeyer, Michael F.; Chen, Shao-Yu; Menkari, Carrie E.; Brenneman, Douglas E.; Sulik, Kathleen K.; Charness, Michael E.

    2003-01-01

    NAPVSIPQ (NAP), an active fragment of the glial-derived activity-dependent neuroprotective protein, is protective at femtomolar concentrations against a wide array of neural insults and prevents ethanol-induced fetal wastage and growth retardation in mice. NAP also antagonizes ethanol inhibition of L1-mediated cell adhesion (ethanol antagonism). We performed an Ala scanning substitution of NAP to determine the role of ethanol antagonism and neuroprotection in NAP preve...

  5. Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes

    OpenAIRE

    Lee, Mi-Jeong; Fried, Susan K.

    2012-01-01

    High concentrations of TNF within obese adipose tissue increase basal lipolysis and antagonize insulin signaling. Adipocytes of the obese are also exposed to elevated levels of glucocorticoids (GCs), which antagonize TNF actions in many cell types. We tested the hypothesis that TNF decreases sensitivity to the antilipolytic effect of insulin and that GCs antagonize this effect in differentiated human adipocytes. Lipolysis and expression levels of lipolytic proteins were measured after treatin...

  6. Oriana: the voice and the silences

    Directory of Open Access Journals (Sweden)

    Mercedes Rosúa

    2007-09-01

    Full Text Available Commentators did their best to bury the late Oriana Fallaci’s ideas and books written since the 11 S under tons of praises to her previous works, and under deep silence or global discrediting her denunciation of Islamic fundamentalism and of terrorist blackmail and all its forms of getting a grip on Europe. Obituary notices avoided carefully the analysis of facts and data brought forward by Oriana in her three last books: The rage and the pride. The power of the reason and Oriana Fallaci’s inter- view with herself. The Apocalypse. But the italian journalist, who past away on 15th Sep- tember 2006, denounced substantiated facts, true dangers and a real collusion of wes- tern sectors-venal, corrupt, fainthearted and ignorant-with the strategy of penetration and manipulation of public opinion of an islamic movement who is the enemy of democracies, Civil Rights, freedom and the western systems of open society.Key words: Oriana Fallaci, Islamic fundamentalism, Defence freedom, Denun- ciation fear, Europe ́s surrender, Terrorism, Western censorship. 

  7. Heteronormativity and Silenced Sexualities at Work

    Directory of Open Access Journals (Sweden)

    Jolanta Reingardė

    2010-01-01

    Full Text Available The paper focuses on workplace as a space in which the normative versions of heterosexuality are produced. Facing the everyday reality of the closet, the majority of homosexual employees constructs and negotiates their silenced sexualities at work. The study is based on 30 in-depth interviews with Lithuanian gays and lesbians carried out within the framework of the EQUAL project “Open and Safe at Work.” The paper discusses how homosexuals confront heteronormativity at work and how it shapes their sexual identity. How is heteronormativity reflected in their choices to stay in the closet or to come out? What are their coping strategies at work? The fear of open discrimination and violence leads to the invisibility of minority sexual orientation at work and the denial of sexuality as irrelevant to the social life. The internal division between sexual (private and social (public is evident in a number of ways. The suppression of the sexual is the most prevalent coping strategy in the heteronormative order.

  8. Improved design of PPRHs for gene silencing.

    Science.gov (United States)

    Rodríguez, Laura; Villalobos, Xenia; Solé, Anna; Lliberós, Carolina; Ciudad, Carlos J; Noé, Véronique

    2015-03-01

    Nowadays, the modulation of gene expression by nucleic acids has become a routine tool in biomedical research for target validation and it is also used to develop new therapeutic approaches. Recently, we developed the so-called polypurine reverse Hoogsteen hairpins (PPRHs) that show high stability and a low immunogenic profile and we demonstrated their efficacy both in vitro and in vivo. In this work, we explored different characteristics of PPRHs to improve their usage as a tool for gene silencing. We studied the role of PPRH length in the range from 20 to 30 nucleotides. We also proved their higher affinity of binding and efficacy on cell viability compared to nonmodified TFOs. To overcome possible off-target effects, we tested wild-type PPRHs, which proved to be capable of binding to their target sequence with more affinity, displaying a higher stability of binding and a higher effect in terms of cell viability. Moreover, we developed a brand new molecule called Wedge-PPRH with the ability to lock the ds-DNA into the displaced structure and proved its efficacy in prostate and breast cancer cell lines. PMID:25615267

  9. Synthetic RNA silencing in bacteria - antimicrobial discovery and resistance breaking

    Directory of Open Access Journals (Sweden)

    James E.M. Stach

    2011-09-01

    Full Text Available The increasing incidence and prevalence of antibiotic resistance in bacteria threatens the antibiotic miracle. Conventional antimicrobial drug development has failed to replace the armamentarium needed to combat this problem, and novel solutions are urgently required. Here we review both natural and synthetic RNA silencing and its potential to provide new antibacterials through improved target selection, evaluation and screening. Furthermore, we focus on synthetic RNA silencers as a novel class of antibacterials and review their unique properties.

  10. Multiple Interpretations of EFL Learners’ Silence in the Iranian Context

    OpenAIRE

    Reza Ghaffar Samar; Elham Yazdanmehr

    2013-01-01

    Attention to silence as part of the communicative discourse was first drawn in Sack’s (1974) paper, in which it was perceived as a linguistic and communicative form, and from the functional point of view as capable of expressing ideational, interpersonal, and textual functions. Awareness of multiple functions of silence including the referential, emotive, conative, phatic, poetic and metalanguage is of greater significance when it comes to language learning settings, where learners from a dif...

  11. Locus-specific ribosomal RNA gene silencing in nucleolar dominance.

    Directory of Open Access Journals (Sweden)

    Michelle S Lewis

    Full Text Available The silencing of one parental set of rRNA genes in a genetic hybrid is an epigenetic phenomenon known as nucleolar dominance. We showed previously that silencing is restricted to the nucleolus organizer regions (NORs, the loci where rRNA genes are tandemly arrayed, and does not spread to or from neighboring protein-coding genes. One hypothesis is that nucleolar dominance is the net result of hundreds of silencing events acting one rRNA gene at a time. A prediction of this hypothesis is that rRNA gene silencing should occur independent of chromosomal location. An alternative hypothesis is that the regulatory unit in nucleolar dominance is the NOR, rather than each individual rRNA gene, in which case NOR localization may be essential for rRNA gene silencing. To test these alternative hypotheses, we examined the fates of rRNA transgenes integrated at ectopic locations. The transgenes were accurately transcribed in all independent transgenic Arabidopsis thaliana lines tested, indicating that NOR localization is not required for rRNA gene expression. Upon crossing the transgenic A. thaliana lines as ovule parents with A. lyrata to form F1 hybrids, a new system for the study of nucleolar dominance, the endogenous rRNA genes located within the A. thaliana NORs are silenced. However, rRNA transgenes escaped silencing in multiple independent hybrids. Collectively, our data suggest that rRNA gene activation can occur in a gene-autonomous fashion, independent of chromosomal location, whereas rRNA gene silencing in nucleolar dominance is locus-dependent.

  12. Between Noise and Silence: Architecture since the 1970s

    OpenAIRE

    Alexandra Brown; Andrew Leach

    2012-01-01

    This essay considers noise in architectural discourse as it might lend form to issues hitherto tabled in rather different terms. We ask what noise offers this discussion or, perhaps better put, what seeing architectural debates in terms of distinctions between noise and silence, random and structured sound, silence as absence and pregnant void might add to disciplinary debates within architectural theory and criticism. By treating these acoustic values analogously rather than literally we wis...

  13. SiRNA Mediated Gene Silencing: A Mini Review

    OpenAIRE

    M.V Jeevitha; S.U Ajisha; Baby Joseph

    2012-01-01

    RNA interference (RNAi) technology has become a novel tool for silencing gene expression in cells or organisms. RNA interference is the process that double-stranded RNA induces the homology-dependent degradation of cognate mRNA mediated by 21-23 nucleotide short interfering RNA (siRNA). RNA interference is a powerful mechanism of gene silencing that underlies many aspects of eukaryotic biology. On the molecular level, RNAi is mediated by a family of ribonucleoprotein (RNP) complexes called R...

  14. Anti-viral RNA silencing: do we look like plants ?

    OpenAIRE

    Lecellier Charles-Henri; Saumet Anne

    2006-01-01

    Abstract The anti-viral function of RNA silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. Because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. It appears that, whereas the anti-viral process seems to ...

  15. Sir- and silencer-independent disruption of silencing in Saccharomyces by Sas10p.

    OpenAIRE

    Kamakaka, R T; Rine, J

    1998-01-01

    A promoter fusion library of Saccharomyces cerevisiae genes was used to exploit phenotypes associated with altered protein dosage. We identified a novel gene, SAS10, by the ability of Sas10p, when overproduced, to disrupt silencing. The predicted Sas10p was 70,200 kD and strikingly rich in charged amino acids. Sas10p was exclusively nuclear in all stages of the cell cycle. Overproduction of Sas10p caused derepression of mating type genes at both HML and HMR, as well as of URA3, TRP1, and ADE2...

  16. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver

    DEFF Research Database (Denmark)

    Elmen, Joachim; Lindow, Morten; Silahtaroglu, Asli; Bak, Mads; Christensen, Mette; Lind-Thomsen, Allan; Hedtjarn, Maj; hansen, jens bo; Hansen, Henrik Freydenlund; Straarup, Ellen Marie; McCullagh, Keith; Keraney, Phil; Kauppinen, Markus Sakari

    2008-01-01

    the LNA-antimiR in mouse liver cells, which was accompanied by markedly reduced hybridization signals for mature miR-122 in treated mice. Functional antagonism of miR-122 was inferred from a low cholesterol phenotype and derepression within 24 h of 199 liver mRNAs showing significant enrichment for mi......MicroRNA-122 (miR-122) is an abundant liver-specific miRNA, implicated in fatty acid and cholesterol metabolism as well as hepatitis C viral replication. Here, we report that a systemically administered 16-nt, unconjugated LNA (locked nucleic acid)- antimiR oligonucleotide complementary to the 5......’end of miR-122 leads to specific, dose-dependent silencing of miR-122 and shows no hepatotoxicity in mice. Antagonism of miR-122 is due to formation of stable heteroduplexes between the LNA-antimiR and miR-122 as detected by northern analysis. Fluorescence in situ hybridization demonstrated uptake of...

  17. SiRNA Mediated Gene Silencing: A Mini Review

    Directory of Open Access Journals (Sweden)

    M.V. Jeevitha

    2012-12-01

    Full Text Available RNA interference (RNAi technology has become a novel tool for silencing gene expression in cells or organisms. RNA interference is the process that double-stranded RNA induces the homology-dependent degradation of cognate mRNA mediated by 21-23 nucleotide short interfering RNA (siRNA. RNA interference is a powerful mechanism of gene silencing that underlies many aspects of eukaryotic biology. On the molecular level, RNAi is mediated by a family of ribonucleoprotein (RNP complexes called RNA-Induced Silencing Complexes (RISCs, which can be programmed to target virtually any nucleic acid sequence for silencing. The ability of RISC to locate target RNAs been co-opted by evolution many times to generate a broad spectrum of gene silencing pathways. The study about the Silencing of gene expression by siRNA is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. In this study, the applications of siRNA expressing recombinant adenovirus system in plants, animals and in cancer gene therapy are given importance with its modifications

  18. Things talked about while we remain silence and things we’re silence about while talking: The starting assumptions for an anthropology of silence about the nearest past

    Directory of Open Access Journals (Sweden)

    Đerić Gordana

    2007-01-01

    Full Text Available Wars of the last decade of the 20th century in former Yugoslavia have brought the whole region into the center of media attention and, accordingly, have aroused interest of the western academic theory. Since the latest ′discovery of the Balkans′ was brought into being precisely due to wars, one shouldn’t be surprised to find that many academic approaches to questions of Yugoslavia dismemberment are biased, superficial or exotic. On the other hand, Serbian academic auditorium was far from being active in elaborating questions of its own contemporality and closest past - for various reasons, but mostly because of its detachment from systematic explorations. Thus, acknowledgement and presentations of mentioned issues were left to be the job of media publicists, others outside of academic community or were left to be treated in the time to come. Domestic scholars were rarely intrigued to deal with these matters, despite the fact that images of recent wars were often built on stereotypes and propaganda and that the formed knowledge of the entire subject suffered from severe simplification. The themes of great violence were particularly avoided which left some of the crucial war events out of the academic focus - the reason being, very probably, the estimation that what made Serbia and the region worldwide known is best to be forgotten. Contemporary academic silence on recent wars, in retrospection, could easily be placed within the continuum of silence during the socialist period and war which preceded it. Having all mentioned in mind, this paper not only investigates reasons for avoiding the issues of the nearest past and influences of silence in socialism on what came afterwards, but also highlights the importance of exploring semantics and functions of silence and silencing in recent wars, as well as the relationship between silence and social memory constructions.

  19. Molecular mechanism of RNA silencing suppression mediated by p19 protein of tombusviruses

    OpenAIRE

    Lakatos, Lóránt; Szittya, György; Silhavy, Dániel; Burgyán, József

    2004-01-01

    RNA silencing is an evolutionarily conserved surveillance system that occurs in a broad range of eukaryotic organisms. In plants, RNA silencing acts as an antiviral system; thus, successful virus infection requires suppression of gene silencing. A number of viral suppressors have been identified so far; however, the molecular bases of silencing suppression are still poorly understood. Here we show that p19 of Cymbidium ringspot virus (CymRSV) inhibits RNA silencing via its small RNA-binding a...

  20. RNA Silencing in Aspergillus nidulans Is Independent of RNA-Dependent RNA Polymerases

    OpenAIRE

    Hammond, T. M.; Keller, N P

    2005-01-01

    The versatility of RNA-dependent RNA polymerases (RDRPs) in eukaryotic gene silencing is perhaps best illustrated in the kingdom Fungi. Biochemical and genetic studies of Schizosaccharomyces pombe and Neurospora crassa show that these types of enzymes are involved in a number of fundamental gene-silencing processes, including heterochromatin regulation and RNA silencing in S. pombe and meiotic silencing and RNA silencing in N. crassa. Here we show that Aspergillus nidulans, another model fung...

  1. Defective RNA processing enhances RNA silencing and influences flowering of Arabidopsis

    OpenAIRE

    Herr, Alan J.; Molnàr, Attila; Jones, Alex; Baulcombe, David C.

    2006-01-01

    Many eukaryotic cells use RNA-directed silencing mechanisms to protect against viruses and transposons and to suppress endogenous gene expression at the posttranscriptional level. RNA silencing also is implicated in epigenetic mechanisms affecting chromosome structure and transcriptional gene silencing. Here, we describe enhanced silencing phenotype (esp) mutants in Arabidopsis thaliana that reveal how proteins associated with RNA processing and 3′ end formation can influence RNA silencing. T...

  2. Export of RNA silencing from C. elegans tissues does not require the RNA channel SID-1

    OpenAIRE

    Jose, Antony M.; Smith, Jessica J.; Hunter, Craig P.

    2009-01-01

    Double-stranded RNA (dsRNA) triggers RNA interference (RNAi) to silence genes of matching sequence. In some animals this experimentally induced silencing is transported between cells, and studies in the nematode Caenorhabditis elegans have shown that the dsRNA channel SID-1 is required for the import of such transported silencing signals. Gene silencing can also be triggered by endogenously expressed RNAi triggers, but it is unknown whether such silencing is transported between cells. Here, w...

  3. Retrovirus silencer blocking by the cHS4 insulator is CTCF independent

    OpenAIRE

    Yao, Shuyuan; Osborne, Cameron S; Bharadwaj, Rikki R.; Pasceri, Peter; Sukonnik, Tanya; Pannell, Dylan; Recillas-Targa, Félix; West, Adam G.; Ellis, James

    2003-01-01

    Silencing of retrovirus vectors poses a significant obstacle to genetic manipulation of stem cells and their use in gene therapy. We describe a mammalian silencer blocking assay using insulator elements positioned between retrovirus silencer elements and an LCRβ-globin reporter transgene. In transgenic mice, we show that retrovirus silencers are blocked by the cHS4 insulator. Silencer blocking is independent of the CTCF binding site and is most effective when flanking the internal reporter tr...

  4. Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

    Directory of Open Access Journals (Sweden)

    MIKI TSUJITA

    2007-01-01

    Full Text Available Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C0(2. In the other experiment, apneic threshold PaC0(2 was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit

  5. A Comparative Study on Performance Parameters of a Conventional Silencer versus Helmholtz Silencer Implemented On A 100cc Motorcycle

    OpenAIRE

    Saurabh Jadhav; Apoorv Prem

    2014-01-01

    Automotive noise and pollution control are critical fields of study and research in recent years. Researchers all across the globe are focusing on making vehicles environmentally friendly by reducing sound and air pollution achieved through implementing various modern technologies. This paper concentrates on the study of noise and pollution performance of a 100cc motorbike on a custom fabricated Helmholtz silencer over a conventional silencer.

  6. The Enamovirus P0 protein is a silencing suppressor which inhibits local and systemic RNA silencing through AGO1 degradation

    Energy Technology Data Exchange (ETDEWEB)

    Fusaro, Adriana F. [University of Sydney, NSW 2006 (Australia); CSIRO Plant Industry, Canberra, P.O. Box 1600, ACT 2601 (Australia); Correa, Regis L. [CSIRO Plant Industry, Canberra, P.O. Box 1600, ACT 2601 (Australia); Depto. de Virologia, IMPPG, UFRJ, 21941-902 (Brazil); Nakasugi, Kenlee; Jackson, Craig [University of Sydney, NSW 2006 (Australia); Kawchuk, Lawrence [Research Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J4B1 (Canada); Vaslin, Maite F.S. [Depto. de Virologia, IMPPG, UFRJ, 21941-902 (Brazil); Waterhouse, Peter M., E-mail: peter.waterhouse@sydney.edu.au [University of Sydney, NSW 2006 (Australia); CSIRO Plant Industry, Canberra, P.O. Box 1600, ACT 2601 (Australia)

    2012-05-10

    The P0 protein of poleroviruses and P1 protein of sobemoviruses suppress the plant's RNA silencing machinery. Here we identified a silencing suppressor protein (SSP), P0{sup PE}, in the Enamovirus Pea enation mosaic virus-1 (PEMV-1) and showed that it and the P0s of poleroviruses Potato leaf roll virus and Cereal yellow dwarf virus have strong local and systemic SSP activity, while the P1 of Sobemovirus Southern bean mosaic virus supresses systemic silencing. The nuclear localized P0{sup PE} has no discernable sequence conservation with known SSPs, but proved to be a strong suppressor of local silencing and a moderate suppressor of systemic silencing. Like the P0s from poleroviruses, P0{sup PE} destabilizes AGO1 and this action is mediated by an F-box-like domain. Therefore, despite the lack of any sequence similarity, the poleroviral and enamoviral SSPs have a conserved mode of action upon the RNA silencing machinery.

  7. Irreversible H2-antagonism of the four isomeric butyl analogues of mifentidine.

    Science.gov (United States)

    Bastiaans, H M; Donetti, A; Kramer, K; Bietti, G; Cereda, E; Dubini, D; Mondini, M; Bast, A; Timmerman, H

    1990-04-01

    It has been hypothesized that bidentate hydrogen bonding plays an important role in the interaction of imidazolylphenylformamidines with the H2-receptor. The present study, in which the degree of pseudo-irreversible H2-antagonism of the four isomeric butyl substituted mifentidine analogues was determined on the spontaneously beating right atrium of the male guinea-pig, lends further support to this hypothesis. In solution the EE/EZ ratio is different for the four isomeric butylated mifentidine analogues. The rank order of the percentage of E,E conformation, which favors a bidentate interaction, of the formamidine moiety parallels the rank order of pseudo-irreversible H2-antagonism. PMID:1973582

  8. On the robustness of SAC silencing in closed mitosis

    Science.gov (United States)

    Ruth, Donovan; Liu, Jian

    Mitosis equally partitions sister chromatids to two daughter cells. This is achieved by properly attaching these chromatids via their kinetochores to microtubules that emanate from the spindle poles. Once the last kinetochore is properly attached, the spindle microtubules pull the sister chromatids apart. Due to the dynamic nature of microtubules, however, kinetochore-microtubule attachment often goes wrong. When this erroneous attachment occurs, it locally activates an ensemble of proteins, called the spindle assembly checkpoint proteins (SAC), which halts the mitotic progression until all the kinetochores are properly attached by spindle microtubules. The timing of SAC silencing thus determines the fidelity of chromosome segregation. We previously established a spatiotemporal model that addresses the robustness of SAC silencing in open mitosis for the first time. Here, we focus on closed mitosis by examining yeast mitosis as a model system. Though much experimental work has been done to study the SAC in cells undergoing closed mitosis, the processes responsible are not well understood. We leverage and extend our previous model to study SAC silencing mechanism in closed mitosis. We show that a robust signal of the SAC protein accumulation at the spindle pole body can be achieved. This signal is a nonlinear increasing function of number of kinetochore-microtubule attachments, and can thus serve as a robust trigger to time the SAC silencing. Together, our mechanism provides a unified framework across species that ensures robust SAC silencing and fidelity of chromosome segregation in mitosis. Intramural research program in NHLBI at NIH.

  9. Precedents and consequences of prosocial behaviors of voice and silence

    Directory of Open Access Journals (Sweden)

    Alicia Omar

    2015-09-01

    Full Text Available Prosocial behavior is that which that encourages solidarity and harmony in interpersonal relationships, and produce personal or collective benefits. Although early research on job prosociality was focused on the study of conventional behaviors such as help, courtesy and sportsmanship, the identification and operationalization of new dimensions is rapidly expanding this nomological network. Such is the case of prosocial voice and prosocial silence, recently introduced in the scientific literature. The aim of this study is to explore possible relationships between employee’s voice and employee’s silence, and their personality structure; and examine the role of interpersonal justice perceptions on such relationships. We worked with a sample of 316 employees- aged 37 years and holding a 4.2-year signority working at public and private companies in southern and central Rosario (Argentina. The subjects completed Colquitt’ Justice Organizational Scale, Eysenck Personality Questionnaire, and Van Dyne’s Prosocial Voice and Prosocial Silence Scales. Extraversion and neuroticism emerged as the strongest predictors of prosocial voice and prosocial silence, respectively. Interpersonal justice perceptions emerged as moderators of the ‘natural’ tendency of extraverted workers to engage in prosocial voice, and emotionally controlled workers to engage in prosocial silence. Such findings would indicate that the promotion of high levels of interpersonal justice on job contexts could help workers to engage in more prosocial behavior with positive effects for the organization. 

  10. Anti-viral RNA silencing: do we look like plants ?

    Directory of Open Access Journals (Sweden)

    Lecellier Charles-Henri

    2006-01-01

    Full Text Available Abstract The anti-viral function of RNA silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. Because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. It appears that, whereas the anti-viral process seems to be similarly conserved from plants to insects, even in worms, RNA silencing does influence the replication of mammalian viruses but in a particular mode: micro(miRNAs, endogenous small RNAs naturally implicated in translational control, rather than virus-derived small interfering (siRNAs like in other organisms, are involved. In fact, these recent studies even suggest that RNA silencing may be beneficial for viral replication. Accordingly, several large DNA mammalian viruses have been shown to encode their own miRNAs. Here, we summarize the seminal studies that have implicated RNA silencing in viral infection and compare the different eukaryotic responses.

  11. Is the Efficiency of RNA Silencing Evolutionarily Regulated?

    Science.gov (United States)

    Ui-Tei, Kumiko

    2016-01-01

    Small interfering RNAs (siRNAs) and microRNAs (miRNAs) regulate gene expression in a sequence-specific manner. Genes with partial complementarity to siRNA/miRNA sequences in their 3'-untranslated regions (UTRs) are suppressed by a mechanism referred to as the siRNA off-target effect or miRNA-mediated RNA silencing. However, the determinants of such RNA silencing efficiency are poorly understood. Previously, I and co-workers reported that the efficiency of RNA silencing is strongly correlated with the thermodynamic stability of base pairing in the duplex formed within an siRNA/miRNA and between the seed region and its target mRNA. In this review, I first summarize our previous studies that identified the thermodynamic parameter to estimate the silencing efficiency using the calculated base pairing stability: siRNAs downregulate the expression of off-target genes depending on the stability of binding between the siRNA seed region (nucleotides 2-8) and off-target mRNAs, and miRNAs downregulate target mRNA expression depending on the stability of the duplex formed between the 5' terminus of the miRNA and its target mRNA. I further discuss the possibility that such thermodynamic features of silencing efficiency may have arisen during evolution with increasing body temperature in various organisms. PMID:27187367

  12. The epigenetic modifier PRDM5 functions as a tumor suppressor through modulating WNT/β-catenin signaling and is frequently silenced in multiple tumors.

    Directory of Open Access Journals (Sweden)

    Xing-sheng Shu

    Full Text Available BACKGROUND: PRDM (PRDI-BF1 and RIZ domain containing proteins are zinc finger proteins involved in multiple cellular regulations by acting as epigenetic modifiers. We studied a recently identified PRDM member PRDM5 for its epigenetic abnormality and tumor suppressive functions in multiple tumorigeneses. METHODOLOGY/PRINCIPAL FINDINGS: Semi-quantitative RT-PCR showed that PRDM5 was broadly expressed in human normal tissues, but frequently silenced or downregulated in multiple carcinoma cell lines due to promoter CpG methylation, including 80% (4/5 nasopharyngeal, 44% (8/18 esophageal, 76% (13/17 gastric, 50% (2/4 cervical, and 25% (3/12 hepatocellular carcinoma cell lines, but not in any immortalized normal epithelial cell lines. PRDM5 expression could be restored by 5-aza-2'-deoxycytidine demethylation treatment in silenced cell lines. PRDM5 methylation was frequently detected by methylation-specific PCR (MSP in multiple primary tumors, including 93% (43/46 nasopharyngeal, 58% (25/43 esophageal, 88% (37/42 gastric and 63% (29/46 hepatocellular tumors. PRDM5 was further found a stress-responsive gene, but its response was impaired when the promoter was methylated. Ectopic PRDM5 expression significantly inhibited tumor cell clonogenicity, accompanied by the inhibition of TCF/β-catenin-dependent transcription and downregulation of CDK4, TWIST1 and MDM2 oncogenes, while knocking down of PRDM5 expression lead to increased cell proliferation. ChIP assay showed that PRDM5 bound to its target gene promoters and suppressed their transcription. An inverse correlation between the expression of PRDM5 and activated β-catenin was also observed in cell lines. CONCLUSIONS/SIGNIFICANCE: PRDM5 functions as a tumor suppressor at least partially through antagonizing aberrant WNT/β-catenin signaling and oncogene expression. Frequent epigenetic silencing of PRDM5 is involved in multiple tumorigeneses, which could serve as a tumor biomarker.

  13. Structure and Gene-Silencing Mechanisms of Small Noncoding RNAs

    Science.gov (United States)

    Chu, Chia-Ying; Rana, Tariq M.

    Small (19-31-nucleotides) noncoding RNAs were identified in the past 10 years for their distinct function in gene silencing. The best known gene-silencing phenomenon, RNA interference (RNAi), is triggered in a sequence-specific manner by endogenously produced or exogenously introduced small doubled-stranded RNAs. As knowledge of the structure and function of the RNAi machinery has expanded, this phenomenon has become a powerful tool for biochemical research; it has enormous potential for therapeutics. This chapter summarizes significant aspects of three major classes of small noncoding, regulatory RNAs: small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). Here, we focus on the biogenesis of these small RNAs, their structural features and coupled effectors as well as the mechanisms of each small regulatory RNA pathway which reveal fascinating ways by which gene silencing is controlled and fine-tuned at an epigenetic level.

  14. RNA silencing can explain chlorotic infection patterns on plant leaves

    Directory of Open Access Journals (Sweden)

    Hogeweg Paulien

    2008-11-01

    Full Text Available Abstract Background RNA silencing has been implicated in virus symptom development in plants. One common infection symptom in plants is the formation of chlorotic tissue in leaves. Chlorotic and healthy tissue co-occur on a single leaf and form patterns. It has been shown that virus levels in chlorotic tissue are high, while they are low in healthy tissue. Additionally, the presence of siRNAs is confined to the chlorotic spots and the boundaries between healthy and infected tissue. These results strongly indicate that the interaction between virus growth and RNA silencing plays a role in the formation of infection patterns on leaves. However, how RNA silencing leads to the intricate patterns is not known. Results Here we elucidate the mechanisms leading to infection patterns and the conditions which lead to the various patterns observed. We present a modeling approach in which we combine intra- and inter-cellular dynamics of RNA silencing and viral growth. We observe that, due to the spread of viruses and the RNA silencing response, parts of the tissue become infected while other parts remain healthy. As is observed in experiments high virus levels coincide with high levels of siRNAs, and siRNAs are also present in the boundaries between infected and healthy tissue. We study how single- and double-stranded cleavage by Dicer and amplification by RNA-dependent RNA polymerase can affect the patterns formed. Conclusion This work shows that RNA silencing and virus growth within a cell, and the local spread of virions and siRNAs between cells can explain the heterogeneous spread of virus in leaf tissue, and therewith the observed infection patterns in plants.

  15. FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function

    OpenAIRE

    Jensen, Kim Steen; Binderup, Tina; Jensen, Klaus Thorleif; Therkelsen, Ib; Borup, Rehannah; Nilsson, Elise; Multhaupt, Hinke; Bouchard, Caroline; Quistorff, Bjørn; Kjær, Andreas; Landberg, Göran; Staller, Peter

    2011-01-01

    This paper characterizes FoxO3A as required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production. Mechanistically, FoxO3A is shown to promote hypoxic cell survival by directly antagonizing c-Myc at nuclear encoded mitochondrial genes.

  16. A `Clicked' Tetrameric Hydroxamic Acid Glycopeptidomimetic Antagonizes Sugar-Lectin Interactions On The Cellular Level

    Science.gov (United States)

    Zhang, Hai-Lin; Zang, Yi; Xie, Juan; Li, Jia; Chen, Guo-Rong; He, Xiao-Peng; Tian, He

    2014-07-01

    A tetrameric N-acetyl galactosaminyl (GalNAc) peptidomimetic was constructed by N-acetylation of repeating proline-based hydroxamic acid units, followed by a convergent `click chemistry' coupling. This novel glycopeptidomimetic was determined to effectively antagonize the interaction between a transmembrane hepatic lectin and GalNAc on the cellular level.

  17. The mechanism of the antagonism by naloxone of acute alcohol intoxication.

    OpenAIRE

    Badawy, A. A.; Evans, M

    1981-01-01

    Naloxone lowers blood-ethanol concentration and causes a simultaneous reversal of the disturbances in the redox states of the hepatic nicotinamide-adenine dinucleotide (phosphate) couples in acutely-ethanol-intoxicated rats. It is suggested that these effects of naloxone form the basis of its antagonism of acute alcohol intoxication.

  18. Impairments of exploration and memory after systemic or prelimbic D1-receptor antagonism in rats

    DEFF Research Database (Denmark)

    Clausen, Bettina; Schachtman, Todd R.; Mark, Louise T.;

    2011-01-01

    D1-receptor antagonism is known to impair rodent memory but also inhibits spontaneous exploration of stimuli to be remembered. Hypo-exploration could contribute to impaired memory by influencing event processing. In order to explore this effect, the D1 receptor antagonist, SCH23390, was administe...

  19. Identifizierung und Charakterisierung von Silencing Suppressoren in Arabidopsis

    OpenAIRE

    Thran, Moritz

    2013-01-01

    Post-transkriptionelles gene silencing (PTGS) kann ein limitierender Faktor für die Expression von Transgenen sein. Transgene mRNAs können von der RNA-DEPENDENT RNA POLYMERASE 6 (RDR6) erkannt werden, was die Synthese doppelsträngiger RNA (dsRNA) initiiert und die Akkumulation von small interfering RNAs (siRNAs) zur Folge hat. Diese vermitteln die sequenzspezifische endonukleolytische Spaltung einer Ziel-mRNA und verhindern somit deren Akkumulation. Für die Initiierung des Transgen Silencing ...

  20. Between Noise and Silence: Architecture since the 1970s

    Directory of Open Access Journals (Sweden)

    Alexandra Brown

    2012-11-01

    Full Text Available This essay considers noise in architectural discourse as it might lend form to issues hitherto tabled in rather different terms. We ask what noise offers this discussion or, perhaps better put, what seeing architectural debates in terms of distinctions between noise and silence, random and structured sound, silence as absence and pregnant void might add to disciplinary debates within architectural theory and criticism. By treating these acoustic values analogously rather than literally we wish to suggest that reading the late postmodern moment through this filter opens out new possibilities for a critical assessment of this period and its present-day legacies.

  1. Two classes of silencing RNAs move between C. elegans tissues

    OpenAIRE

    Jose, Antony Merlin; Garcia, Giancarlo; Hunter, Craig P.

    2011-01-01

    Summary Organism-wide RNA interference (RNAi) is due to the transport of mobile silencing RNA throughout the organism but the identities of these mobile RNA species in animals are unknown. Here we present genetic evidence that both the initial double-stranded RNA (dsRNA), which triggers RNAi, and at least one dsRNA intermediate produced during RNAi can act as or generate mobile silencing RNA in Caenorhabditis elegans. This dsRNA intermediate requires the long dsRNA-binding protein RDE-4, the ...

  2. Novel Sexual-Cycle-Specific Gene Silencing in Aspergillus nidulans

    OpenAIRE

    Czaja, Wioletta; Miller, Karen Y.; Bruce L. Miller

    2013-01-01

    We report a novel sexual-cycle-specific gene-silencing system in the genetic model Aspergillus nidulans. Duplication of the mating type matAHMG gene in this haploid organism triggers Mat-induced silencing (MatIS) of both endogenous and transgenic matA genes, eliminates function of the encoded SRY structural ortholog, and results in formation of barren fruiting bodies. MatIS is spatiotemporally restricted to the prezygotic stage of the sexual cycle and does not interfere with vegetative growth...

  3. Double-Stranded RNA Binding May Be a General Plant RNA Viral Strategy To Suppress RNA Silencing

    OpenAIRE

    Mérai, Zsuzsanna; Kerényi, Zoltán; Kertész, Sándor; Magna, Melinda; Lakatos, Lóránt; Silhavy, Dániel

    2006-01-01

    In plants, RNA silencing (RNA interference) is an efficient antiviral system, and therefore successful virus infection requires suppression of silencing. Although many viral silencing suppressors have been identified, the molecular basis of silencing suppression is poorly understood. It is proposed that various suppressors inhibit RNA silencing by targeting different steps. However, as double-stranded RNAs (dsRNAs) play key roles in silencing, it was speculated that dsRNA binding might be a g...

  4. The Voice of Silence in Communication-from cross-culture perspective

    Institute of Scientific and Technical Information of China (English)

    曹琪雯

    2014-01-01

    This paper makes a study of silence from cross-culture perspective and holds that silence is an indispensable compo-nent of human communication without which the proper decoding of the information would be impossible.

  5. Identification of Pns6, a putative movement protein of RRSV, as a silencing suppressor

    Directory of Open Access Journals (Sweden)

    Lin Qiying

    2010-11-01

    Full Text Available Abstract RNA silencing is a potent antiviral response in plants. As a counterdefense, most plant and some animal viruses encode RNA silencing suppressors. In this study, we showed that Pns6, a putative movement protein of Rice ragged stunt virus (RRSV, exhibited silencing suppressor activity in coinfiltration assays with the reporter green fluorescent protein (GFP in transgenic Nicotiana benthamiana line 16c. Pns6 of RRSV suppressed local silencing induced by sense RNA but had no effect on that induced by dsRNA. Deletion of a region involved in RNA binding abolished the silencing suppressor activity of Pns6. Further, expression of Pns6 enhanced Potato virus × pathogenicity in N. benthamiana. Collectively, these results suggested that RRSV Pns6 functions as a virus suppressor of RNA silencing that targets an upstream step of the dsRNA formation in the RNA silencing pathway. This is the first silencing suppressor to be identified from the genus Oryzavirus.

  6. Gendered Communication in Iranian University Classrooms: The Relationship between Politeness and Silence in Persian Culture

    Directory of Open Access Journals (Sweden)

    Saeedeh Shafiee Nahrkhalaji

    2013-05-01

    Full Text Available This study examined naturally-occurring university classroominteractions at Iranian universities and provided an analysis ofsilence patterns as politeness strategies used by male andfemale students. Since empirical studies of silence inclassroom settings are scarce, this paper aimed to explainsuch phenomena using participant interviews, classroomobservation and detailed discourse analysis of classroominteraction. Silence patterns and their interpretations werescrutinized in these observations and were discussed inrelation to specific conceptualization of politeness anddevices employed to exercise it. The study found that femalesseem to be the most silent in the cross-sex classrooms, whilethe distribution of silence is more nearly equal in the same sexclassrooms. Based on the comments from follow-upinterviews, reasons for intentional silence as a politenessstrategy were categorized into four groups: silence as a face savingstrategy, silence as a ‘don’t do the FTA’ strategy,silence as a power strategy, and silence as an off-recordstrategy.

  7. The Research on the Silence Phenomena of Students in College English Classroom Teaching

    Institute of Scientific and Technical Information of China (English)

    杨六兰

    2015-01-01

    This paper analyzes the reasons that resulted in silence phenomena in college English classroom teaching,and gives some feasible suggestions to break the classroom silence in English classroom teaching.

  8. The preferred route for the degradation of silencing target RNAs in transgenic plants depends on pre-established silencing conditions

    OpenAIRE

    Sanders, Matthew; Lannoo, Nausicaä; Maddelein, Wendy; Depicker, Anna; Van Montagu, Marc; Cornelissen, Marc; Jacobs, John

    2004-01-01

    RNA silencing can be initiated upon dsRNA accumulation and results in homology-dependent degradation of target RNAs mediated by 21–23 nt small interfering RNAs (siRNAs). These small regulatory RNAs can direct RNA degradation via different routes such as the RdRP/Dicer- and the RNA-induced silencing complex (RISC)-catalysed pathways. The relative contribution of both pathways to degradation of target RNAs is not understood. To gain further insight in the process of target selection and degrada...

  9. Involvement of RDR6 in short-range intercellular RNA silencing in Nicotiana benthamiana

    OpenAIRE

    Cheng Qin; Nongnong Shi; Mei Gu; Hang Zhang; Bin Li; Jiajia Shen; Atef Mohammed; Eugene Ryabov; Chunyang Li; Huizhong Wang; Yule Liu; Toba Osman; Manu Vatish; Yiguo Hong

    2012-01-01

    In plants, non-cell autonomous RNA silencing spreads between cells and over long distances. Recent work has revealed insight on the genetic and molecular components essential for cell-to-cell movement of RNA silencing in Arabidopsis. Using a local RNA silencing assay, we report on a distinct mechanism that may govern the short-range (6–10 cell) trafficking of virus-induced RNA silencing from epidermal to neighbouring palisade and spongy parenchyma cells in Nicotiana benthamiana. This process ...

  10. Identification of Pns6, a putative movement protein of RRSV, as a silencing suppressor

    OpenAIRE

    Lin Qiying; Wu Zujian; Hu Meiqun; Cai Lijun; Wang Chunzheng; Du Zhenguo; Wu Jianguo; Li Yi; Xie Lianhui

    2010-01-01

    Abstract RNA silencing is a potent antiviral response in plants. As a counterdefense, most plant and some animal viruses encode RNA silencing suppressors. In this study, we showed that Pns6, a putative movement protein of Rice ragged stunt virus (RRSV), exhibited silencing suppressor activity in coinfiltration assays with the reporter green fluorescent protein (GFP) in transgenic Nicotiana benthamiana line 16c. Pns6 of RRSV suppressed local silencing induced by sense RNA but had no effect on ...

  11. The dynamics and efficacy of antiviral RNA silencing: A model study

    OpenAIRE

    Hogeweg Paulien; Groenenboom Marian AC

    2008-01-01

    Abstract Background Mathematical modeling is important to provide insight in the complicated pathway of RNA silencing. RNA silencing is an RNA based mechanism that is widely used by eukaryotes to fight viruses, and to control gene expression. Results We here present the first mathematical model that combines viral growth with RNA silencing. The model involves a plus-strand RNA virus that replicates through a double-strand RNA intermediate. The model of the RNA silencing pathway consists of cl...

  12. A Multifunctional Protein Encoded by Turkey Herpesvirus Suppresses RNA Silencing in Nicotiana benthamiana▿

    OpenAIRE

    Jing, Xiu-li; Fan, Mei-na; Jia, Gang; Liu, Lan-wei; Lin MA; Zheng, Cheng-Chao; Zhu, Xiao-Ping; Liu, Hong-Mei; Wang, Xiao-Yun

    2011-01-01

    Many plant and animal viruses counteract RNA silencing-mediated defense by encoding diverse RNA silencing suppressors. We characterized HVT063, a multifunctional protein encoded by turkey herpesvirus (HVT), as a silencing suppressor in coinfiltration assays with green fluorescent protein transgenic Nicotiana benthamiana line 16c. Our results indicated that HVT063 could strongly suppress both local and systemic RNA silencing induced by either sense RNA or double-stranded RNA (dsRNA). HVT063 co...

  13. Analysis of hairpin RNA transgene-induced gene silencing in Fusarium oxysporum

    OpenAIRE

    Schumann, Ulrike; Smith, Neil A; Kazan, Kemal; Ayliffe, Michael; Wang, Ming-Bo

    2013-01-01

    Background Hairpin RNA (hpRNA) transgenes can be effective at inducing RNA silencing and have been exploited as a powerful tool for gene function analysis in many organisms. However, in fungi, expression of hairpin RNA transcripts can induce post-transcriptional gene silencing, but in some species can also lead to transcriptional gene silencing, suggesting a more complex interplay of the two pathways at least in some fungi. Because many fungal species are important pathogens, RNA silencing is...

  14. SERRATE is required for intron suppression of RNA silencing in Arabidopsis

    OpenAIRE

    Christie, Michael; Carroll, Bernard J.

    2011-01-01

    Transposons and viruses are generally devoid of introns and are prime targets for small interfering RNAs (siRNAs) and RNA silencing. Conversely, endogenous genes often contain introns and are not usually subjected to post-transcriptional gene silencing by siRNAs. In a recent study, we reported that efficient intron splicing directly suppresses siRNA biogenesis and RNA silencing of a Green Fluorescence Protein (GFP) transgene. Splicing-mediated suppression of GFP silencing was dependent on ABH...

  15. Modification of Small RNAs Associated with Suppression of RNA Silencing by Tobamovirus Replicase Protein▿

    OpenAIRE

    Vogler, Hannes; Akbergenov, Rashid; Shivaprasad, Padubidri V; Dang, Vy; Fasler, Monika; Kwon, Myoung-Ok; Zhanybekova, Saule; Hohn, Thomas; Heinlein, Manfred

    2007-01-01

    Plant viruses act as triggers and targets of RNA silencing and have evolved proteins to suppress this plant defense response during infection. Although Tobacco mosaic tobamovirus (TMV) triggers the production of virus-specific small interfering RNAs (siRNAs), this does not lead to efficient silencing of TMV nor is a TMV-green fluorescent protein (GFP) hybrid able to induce silencing of a GFP-transgene in Nicotiana benthamiana, indicating that a TMV silencing suppressor is active and acts down...

  16. Dispositives of silence: gender, feminism and Czech literature between 1948 and 1989

    Czech Academy of Sciences Publication Activity Database

    Matonoha, Jan

    London: Routledge, 2014 - (Havelková, H.; Oates-Indruchová, L.), s. 162-187 ISBN 978-0-415-72083-0 Institutional support: RVO:68378068 Keywords : Czech literature * 2nd half of the 20th century * dispositives of silence and silencing * discursive emergence and constitution of silence * injurious identity and wounding attachments * Silence and absenting recognition of gender and feminist issues Subject RIV: AJ - Letters, Mass-media, Audiovision

  17. Love Styles and Self-Silencing in Romantic Relationships

    Science.gov (United States)

    Collins, Kerry A.; Cramer, Kenneth M.; Singleton-Jackson, Jill A.

    2005-01-01

    Six love styles have been theorized to be related to several personality constructs (e.g., self-esteem) (Lee, 1973). Despite the interpersonal nature of love, investigations have yet to evaluate related variables and their association to love styles in romantic relationships. As a stable cognitive schema, silencing the self is proposed to account…

  18. Marie Nimier, au cœur du silence

    Directory of Open Access Journals (Sweden)

    Joëlle Papillon

    2012-01-01

    Full Text Available Dans La Reine du silence, Marie Nimier se confronte à la figure de son père, l’écrivain Roger Nimier, mort lorsqu’elle avait cinq ans. Elle y montre le poids qui pèse sur l’enfant d’écrivain, mais aussi celui de l’héritage du secret familial et de l’injonction au silence. La difficulté de l’élaboration de son récit de filiation se révèle dans les constants recommencements et reformulations, qui constituent la marque de la tension angoissante entre l’obligation de dire et celle de taire. In La Reine du silence, Marie Nimier confronts her father’s memory – the writer Roger Nimier, who died when she was five years old. The novel describes the burden of being a writer’s child, along with that of inheriting family secrets and submitting to a code of silence. The difficulty of recounting her relationship with her late father is evidenced by the narrator’s numerous “false starts” and her constant rewritings. The hesitant nature of the narration captures an anguish born of two irreconcilable obligations : the need to put things into words and the pressure to remain silent.

  19. Breaking the Silence: Helping Battered Moms and Their Children.

    Science.gov (United States)

    Texas Child Care, 2000

    2000-01-01

    Discusses issues of domestic violence to help child caregivers care for children more effectively. Considers the causes of domestic violence and its impact on children and families, and offers resources for more information as well as suggestions for helping an abused person get help. Includes lists of "Do's and don'ts for breaking the silence"…

  20. Bureaucratic Constructions of Sexual Diversity: "Sensitive", "Controversial" and Silencing

    Science.gov (United States)

    Ullman, Jacqueline; Ferfolja, Tania

    2015-01-01

    National research illustrates the high degree of discrimination that prevails against lesbian, gay, bisexual, transgender and queer (LGBTQ) students resulting in diminished educational outcomes, both academic and social. This phenomenon is influenced by the prevalence of whole-school silences around LGBTQ topics in many Australian schools. This…

  1. Breaking Classroom Silences: A View from Linguistic Ethnography

    Science.gov (United States)

    Rampton, Ben; Charalambous, Constadina

    2016-01-01

    This paper addresses potentially problematic classroom episodes in which someone foregrounds a social division that is normally taken for granted. It illustrates the way in which linguistic ethnography can unpack the layered processes that collide in the breaking of silence, showing how linguistic form and practice, individual positioning, local…

  2. Breaking the Silence Surrounding Mental Health on Campus

    Science.gov (United States)

    Roper, Larry D.

    2013-01-01

    Mentally ill students are able to participate in higher education at unprecedented rates. While colleges and universities have been responsive to the therapeutic needs, we have failed to successfully create supportive campus climates. Campus leaders are challenged to demonstrate ethical leadership that breaks the silence and confronts the stigma…

  3. Mobile gene silencing in Arabidopsis is regulated by hydrogen peroxide

    Directory of Open Access Journals (Sweden)

    Dacheng Liang

    2014-12-01

    Full Text Available In plants and nematodes, RNAi can spread from cells from which it is initiated to other cells in the organism. The underlying mechanism controlling the mobility of RNAi signals is not known, especially in the case of plants. A genetic screen designed to recover plants impaired in the movement but not the production or effectiveness of the RNAi signal identified RCI3, which encodes a hydrogen peroxide (H2O2-producing type III peroxidase, as a key regulator of silencing mobility in Arabidopsis thaliana. Silencing initiated in the roots of rci3 plants failed to spread into leaf tissue or floral tissue. Application of exogenous H2O2 reinstated the spread in rci3 plants and accelerated it in wild-type plants. The addition of catalase or MnO2, which breaks down H2O2, slowed the spread of silencing in wild-type plants. We propose that endogenous H2O2, under the control of peroxidases, regulates the spread of gene silencing by altering plasmodesmata permeability through remodelling of local cell wall structure, and may play a role in regulating systemic viral defence.

  4. Organizational Justice As a Predictor of Organizational Silence

    Science.gov (United States)

    Tan, Çetin

    2014-01-01

    In this study, relation between teachers' perception for organizational justice and their organizational silence was examined. Sample of this study consists of 300 teachers who work at elementary schools in Siirt. Relational Scanning model was utilized in performance of this study. In this study, Organizational Justice Scale and…

  5. Disease-Causing Allele-Specific Silencing by RNA Interference

    Directory of Open Access Journals (Sweden)

    Hirohiko Hohjoh

    2013-04-01

    Full Text Available Small double-stranded RNAs (dsRNAs of approximately 21-nucleotides in size, referred to as small interfering RNA (siRNA duplexes, can induce sequence-specific posttranscriptional gene silencing, or RNA interference (RNAi. Since chemically synthesized siRNA duplexes were found to induce RNAi in mammalian cells, RNAi has become a powerful reverse genetic tool for suppressing the expression of a gene of interest in mammals, including human, and its application has been expanding to various fields. Recent studies further suggest that synthetic siRNA duplexes have the potential for specifically inhibiting the expression of an allele of interest without suppressing the expression of other alleles, i.e., siRNA duplexes likely confer allele-specific silencing. Such gene silencing by RNAi is an advanced technique with very promising applications. In this review, I would like to discuss the potential utility of allele-specific silencing by RNAi as a therapeutic method for dominantly inherited diseases, and describe possible improvements in siRNA duplexes for enhancing their efficacy.

  6. Studies of the silencing of Baculovirus DNA binding protein

    NARCIS (Netherlands)

    Quadt, I.; Lent, van J.W.M.; Knebel-Morsdorf, D.

    2007-01-01

    Baculovirus DNA binding protein (DBP) binds preferentially single-stranded DNA in vitro and colocalizes with viral DNA replication sites. Here, its putative role as viral replication factor has been addressed by RNA interference. Silencing of DBP in Autographa californica multiple nucleopolyhedrovir

  7. A reciprocal identity method for large silencer analysis

    Science.gov (United States)

    Zhou, L.; Wu, T. W.; Ruan, K.; Herrin, D. W.

    2016-03-01

    Conventional techniques used in the boundary element method for evaluating muffler transmission loss have been limited by the cutoff frequency of the inlet and outlet ducts. Even though the boundary element method itself is a truly three-dimensional analysis tool, it has not been effectively used on large silencers due to the large inlet and outlet cross sections. In this paper, a numerical technique based on the reciprocal identity and the boundary element impedance matrix is proposed as a post-processing filter to extract the transmission loss of large silencers at all frequencies. Each reciprocal identity couples two different sound fields on the same silencer geometry. The first sound field has the analytical modal expansion in the inlet and outlet ducts, while the second sound field is the boundary element solution associated with a random boundary condition set. Depending on how many modes exist in the inlet and outlet ducts at a certain frequency, a minimum number of random boundary condition sets must be applied to the boundary element model. The boundary element impedance matrix provides more than enough such solution sets for the reciprocal identity coupling. The overdetermined system is then solved by a least-squares procedure. The proposed method is verified by comparing to the analytical solutions of a simple expansion chamber and a round bar silencer.

  8. Tacit Authorization : A Legal Solution for Administrative Silence

    NARCIS (Netherlands)

    Hoogstra, Nicole; de Graaf, K.J.

    2016-01-01

    This article discusses one of the current legal instruments to stimulate timely decision-making by administrative authorities, namely the ‘Lex silencio positivo’ or the ‘Silence is Consent’ rule. Tacit authorization prescribes that the license sought by the applicant will be granted automatically if

  9. Toward a science of silence: The consequences of leaving a memory unsaid

    DEFF Research Database (Denmark)

    Stone, Charles; Coman, Alin; Brown, Adam;

    2012-01-01

    , whether the silence is intentional or unintentional, and whether the silenced memory is related or unrelated to the memories emerging in a conversation. These factors appear to be critical when considering the mnemonic consequences. Moreover, the influence of silence on memory varies between speaker and...

  10. Importance of coat protein and RNA silencing in satellite RNA/virus interactions

    Science.gov (United States)

    RNA silencing is a major defense mechanism that plants use to fight an invading virus. The silencing suppressor of Turnip crinkle virus (TCV) is the viral coat protein (CP), which obstructs the DCL2/DCL4 silencing pathway. TCV is associated with a virulent satellite RNA (satC) that represses the a...

  11. Trans-specific gene silencing between host and parasitic plants.

    Science.gov (United States)

    Tomilov, Alexey A; Tomilova, Natalia B; Wroblewski, Tadeusz; Michelmore, Richard; Yoder, John I

    2008-11-01

    Species of Orobanchaceae parasitize the roots of nearby host plants to rob them of water and other nutrients. Parasitism can be debilitating to the host plant, and some of the world's most pernicious agricultural pests are parasitic weeds. We demonstrate here that interfering hairpin constructs transformed into host plants can silence expression of the targeted genes in the parasite. Transgenic roots of the hemi-parasitic plant Triphysaria versicolor expressing the GUS reporter gene were allowed to parasitize transgenic lettuce roots expressing a hairpin RNA containing a fragment of the GUS gene (hpGUS). When stained for GUS activity, Triphysaria roots attached to non-transgenic lettuce showed full GUS activity, but those parasitizing transgenic hpGUS lettuce lacked activity in root tissues distal to the haustorium. Transcript quantification indicated a reduction in the steady-state level of GUS mRNA in Triphysaria when they were attached to hpGUS lettuce. These results demonstrate that the GUS silencing signal generated by the host roots was translocated across the haustorium interface and was functional in the parasite. Movement across the haustorium was bi-directional, as demonstrated in double-junction experiments in which non-transgenic Triphysaria concomitantly parasitized two hosts, one transgenic for hpGUS and the other transgenic for a functional GUS gene. Observation of GUS silencing in the second host demonstrated that the silencing trigger could be moved from one host to another using the parasite as a physiological bridge. Silencing of parasite genes by generating siRNAs in the host provides a novel strategy for controlling parasitic weeds. PMID:18643992

  12. Tobacco rattle virus 16K silencing suppressor binds ARGONAUTE 4 and inhibits formation of RNA silencing complexes.

    Science.gov (United States)

    Fernández-Calvino, Lourdes; Martínez-Priego, Llúcia; Szabo, Edit Z; Guzmán-Benito, Irene; González, Inmaculada; Canto, Tomás; Lakatos, Lóránt; Llave, César

    2016-01-01

    The cysteine-rich 16K protein of tobacco rattle virus (TRV), the type member of the genus Tobravirus, is known to suppress RNA silencing. However, the mechanism of action of the 16K suppressor is not well understood. In this study, we used a GFP-based sensor strategy and an Agrobacterium-mediated transient assay in Nicotiana benthamiana to show that 16K was unable to inhibit the activity of existing small interfering RNA (siRNA)- and microRNA (miRNA)-programmed RNA-induced silencing effector complexes (RISCs). In contrast, 16K efficiently interfered with de novo formation of miRNA- and siRNA-guided RISCs, thus preventing cleavage of target RNA. Interestingly, we found that transiently expressed endogenous miR399 and miR172 directed sequence-specific silencing of complementary sequences of viral origin. 16K failed to bind small RNAs, although it interacted with ARGONAUTE 4, as revealed by bimolecular fluorescence complementation and immunoprecipitation assays. Site-directed mutagenesis demonstrated that highly conserved cysteine residues within the N-terminal and central regions of the 16K protein are required for protein stability and/or RNA silencing suppression. PMID:26498945

  13. Antagonism of human formyl peptide receptor 1 with natural compounds and their synthetic derivatives.

    Science.gov (United States)

    Schepetkin, Igor A; Khlebnikov, Andrei I; Kirpotina, Liliya N; Quinn, Mark T

    2016-08-01

    Formyl peptide receptor 1 (FPR1) regulates a wide variety of neutrophil functional responses and plays an important role in inflammation and the pathogenesis of various diseases. To date, a variety of natural and synthetic molecules have been identified as FPR1 ligands. Here, we review current knowledge on natural products and natural product-inspired small molecules reported to antagonize and/or inhibit the FPR1-mediated responses. Based on this literature, additional screening of selected commercially available natural compounds for their ability to inhibit fMLF-induced Ca(2+) mobilization in human neutrophils and FPR1 transfected HL-60 cells, and pharmacophore modeling, natural products with potential as FPR1 antagonists are considered and discussed in this review. The identification and characterization of natural products that antagonize FPR1 activity may have potential for the development of novel therapeutics to limit or alter the outcome of inflammatory processes. PMID:26382576

  14. 'Antagonism' and 'dilution' effects at reducing radionuclide uptake by wood plants

    International Nuclear Information System (INIS)

    Results of an experiment specially designed to decrease cesium 137 and strontium 90 accumulation level in Pinus sylvestris through enriching of radionuclide-contaminated soil with nutrients are discussed. Two experimental approaches were used. One of them - 'antagonism' - is based upon the using of potassium as antagonist of cesium and calcium and magnesium as antagonists of strontium for enrichment of soil. The method of 'dilution' consists of the decreasing of portion of radionuclides in plant biomass by enrichment of soils with microelements. It was determined that the effect of 'antagonism' played a crucial role in blocking of root supply of cesium 137 into trees whole the 'dilution' effect was of prime importance for preventing root uptake of strontium 90. These data demonstrate that it is not correct to transfer mechanically the results of the investigations of growing clean agricultural products to forests

  15. Glucagon antagonism as a potential therapeutic target in type 2 diabetes

    DEFF Research Database (Denmark)

    Bagger, J I; Knop, F K; Holst, Jens Juul; Vilsbøll, T

    2011-01-01

    has been implicated in the development of fasting and postprandial hyperglycaemia. Therefore, new therapeutic agents based on antagonizing glucagon action, and hence blockade of glucagon-induced HGP, could be effective in lowering both fasting and postprandial hyperglycaemia in patients with T2DM....... This review focuses on the mechanism of action, safety and efficacy of glucagon antagonists in the treatment of T2DM and discusses the challenges associated with this new potential antidiabetic treatment modality....

  16. Evaluation of the antagonism of nicotine by mecamylamine and pempidine in the brain

    International Nuclear Information System (INIS)

    Antagonists have been crucial in the characterization of nicotine's pharmacology. Initial evidence for the existence of central nicotinic receptors was based on the fact that nicotine produced a number of behavioral effects that were antagonized by ganglionic blockers that crossed the blood-brain barrier, such as mecamylamine and pempidine. These compounds are thought to be noncompetitive antagonists due to the fact that they do not compete for agonist binding to brain homogenate in vitro. However, pharmacological evidence in support of noncompetitive antagonism is lacking. Dose-response curves for nicotine were determined in the presence of various doses of pempidine for depression of spontaneous activity and antinociception in mice. Pempidine was found to shift the dose response curves for these effects of nicotine in a manner consistent with noncompetitive antagonism. A number of mecamylamine analogs were investigated for antagonism of these central effects of nicotine as well. These studies revealed that the N-, 2-, and 3-methyls were crucial for optimal efficacy and potency and suggests that these compounds possess a specific mechanism of action, possibly involving a receptor. Furthermore, the structure-activity relationships for the mecamylamine analogs were found to be different than that previously reported for the agonists, suggesting that they do not act at the same site. The binding of [3 H]-L-nicotine and [3H]-pempidine was studied in vitro to mouse brain homogentate and in situ to rat brain slices. The in situ binding of [3H]-L-nicotine to rat brain slices was quantitated autoradiographically to discrete brain areas in the presence and absence of 1, 10 and 100 μM nicotine and pempidine. Pempidine did not effectively displace [3H]-L-nicotine binding

  17. FCJ-156 Hacking the Social: Internet Memes, Identity Antagonism, and the Logic of Lulz.

    OpenAIRE

    Ryan M. Milner

    2013-01-01

    4chan and reddit are participatory media collectives undergirded by a “logic of lulz” that favours distanced irony and critique. It often works at the expense of core identity categories like race and gender. However, the logic need not be entirely counterproductive to public discourse. Provided that diverse identities find voice instead of exclusion, these sites may facilitate vibrant, agonistic discussion instead of disenfranchising antagonism. In order to assess this potential for producti...

  18. Genomic conflicts and sexual antagonism in human health: Insights from oxytocin and testosterone

    OpenAIRE

    Mökkönen, Mikael; Crespi, Bernard J.

    2015-01-01

    We review the hypothesized and observed effects of two of the major forms of genomic conflicts, genomic imprinting and sexual antagonism, on human health. We focus on phenotypes mediated by peptide and steroid hormones (especially oxytocin and testosterone) because such hormones centrally mediate patterns of physical and behavioral resource allocation that underlie both forms of conflict. In early development, a suite of imprinted genes modulates the human oxytocinergic system as predicted fr...

  19. Effect of Chronic Endothelin Receptor Antagonism on Cerebrovascular Function in Type 2 Diabetes

    OpenAIRE

    Harris, Alex K; Elgebaly, Mostafa M.; Li, Weiguo; Sachidanandam, Kamakshi; Ergul, Adviye

    2008-01-01

    Diabetes increases the risk of stroke and contributes to poor clinical outcomes in this patient population. Myogenic tone of the cerebral vasculature, including basilar arteries, plays a key role in controlling cerebral blood flow. Increased myogenic tone is ameliorated with ET receptor antagonism in Type 1 diabetes. However, the role of ET-1 and its receptors in cerebrovascular dysfunction in Type-2 diabetes, a common comorbidity in stroke patients, remains poorly elucidated. Therefore, we h...

  20. β-Endorphin Antagonizes the Effects of α-MSH on Food Intake and Body Weight

    OpenAIRE

    Dutia, Roxanne; Meece, Kana; Dighe, Shveta; Kim, Andrea J.; Sharon L Wardlaw

    2012-01-01

    Proopiomelanocortin (POMC) is posttranslationally processed to several peptides including α-MSH, a primary regulator of energy balance that inhibits food intake and stimulates energy expenditure. However, another POMC-derived peptide, β-endorphin (β-EP), has been shown to stimulate food intake. In this study we examined the effects of intracerebroventricular (icv) β-EP on food intake and its ability to antagonize the negative effects of α-MSH on energy balance in male rats. A single icv injec...

  1. Natural Antagonisms: Violence and the Environment in Contemporary Latin American Narrative

    OpenAIRE

    Lee, Diana Dodson

    2015-01-01

    ABSTRACT OF THE DISSERTATIONNatural Antagonisms: Violence and the Environment inContemporary Latin American NarrativebyDiana Lynn Dodson LeeDoctor of Philosophy, Graduate Program in SpanishUniversity of California, Riverside, August 2015 Dr. Raymond Leslie Williams, ChairpersonThis project explores intersections between representations of violence and the environment in contemporary Latin American narrative. I analyze the way in which specific novels represent the wider interconnectedness of ...

  2. Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system

    OpenAIRE

    Schlosburg, Joel E.; Blankman, Jacqueline L.; Long, Jonathan Z.; Daniel K Nomura; Pan, Bin; Kinsey, Steven G.; Nguyen, Peter T.; Ramesh, Divya; Booker, Lamont; Burston, James J; Thomas, Elizabeth A.; Selley, Dana E; Sim-Selley, Laura J; Liu, Qingsong; Lichtman, Aron H.

    2010-01-01

    Prolonged exposure to drugs of abuse, such as cannabinoids and opioids, leads to pharmacological tolerance and receptor desensitization in the nervous system. Here we show that a similar form of functional antagonism is produced by sustained inactivation of monoacylglycerol lipase (MAGL), the principal degradative enzyme for the endocannabinoid 2-arachidonoylglycerol (2-AG). After repeated administration, the MAGL inhibitor JZL184 lost its analgesic activity and produced cross-tolerance to ca...

  3. Ku-deficient yeast strains exhibit alternative states of silencing competence.

    Science.gov (United States)

    Maillet, L; Gaden, F; Brevet, V; Fourel, G; Martin, S G; Dubrana, K; Gasser, S M; Gilson, E

    2001-03-01

    In Saccharomyces cerevisiae, efficient silencer function requires telomere proximity, i.e. compartments of the nucleoplasm enriched in silencing factors. Accordingly, silencers located far from telomeres function inefficiently. We show here that cells lacking yKu balance between two mitotically stable states of silencing competence. In one, a partial delocalization of telomeres and silencing factors throughout the nucleoplasm correlates with enhanced silencing at a non-telomeric locus, while in the other, telomeres retain their focal pattern of distribution and there is no repression at the non-telomeric locus, as observed in wild-type cells. The two states also differ in their level of residual telomeric silencing. These findings indicate the existence of a yKu-independent pathway of telomere clustering and Sir localization. Interestingly, this pathway appears to be under epigenetic control. PMID:11266361

  4. Antagonism between abscisic acid and gibberellins is partially mediated by ascorbic acid during seed germination in rice

    OpenAIRE

    Ye, Nenghui; Zhang, Jianhua

    2012-01-01

    The antagonism between abscisic acid (ABA) and gibberellin (GA) plays a key role in controlling seed germination,1,2 but the mechanism of antagonism during this process is not known. In the associated study,3 we investigated the relationship among ABA, reactive oxygen species (ROS), ascorbic acid (ASC) and GA during rice seed germination. ROS production is reduced by ABA, which hence results in decreasing ASC accumulation during imbibition. GA accumulation was also suppressed by a reduced ROS...

  5. Experimental testing of Mackay's model for functional antagonism in the isolated costo-uterus of the rat.

    OpenAIRE

    Henry, P. J.; Lulich, K M; Paterson, J W

    1985-01-01

    Several key predictions of a recently developed model for functional antagonism (Mackay, 1981) were experimentally tested using the rat isolated costo-uterine preparation. In the presence of the functional antagonist fenoterol (Fen), the functional constants (KAF) for carbachol and oxotremorine (Oxo) were respectively 9.9 and 3.4 fold greater than their corresponding affinity constants (KA). According to Mackay's model for functional antagonism, the higher KAF/KA ratio for carbachol indicates...

  6. Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines

    International Nuclear Information System (INIS)

    Platelets are frequently altered in hepatocellular carcinoma (HCC) patients. Platelet lysates (hPL) can enhance HCC cell growth and decrease apoptosis. The aims were to evaluate whether hPL can modulate the actions of Sorafenib or Regorafenib, two clinical HCC multikinase antagonists. Several human HCC cell lines were grown in the presence and absence of Sorafenib or Regorafenib, with or without hPL. Growth was measured by MTT assay, apoptosis was assessed by Annexin V and by western blot, and autophagy and MAPK growth signaling were also measured by western blot, and migration and invasion were measured by standard in vitro assays. Both Sorafenib and Regorafenib-mediated inhibition of cell growth, migration and invasion were all antagonized by hPL. Drug-mediated apoptosis and decrease in phospho-ERK levels were both blocked by hPL, which also increased anti-apoptotic phospho-STAT, Bax and Bcl-xL levels. Preliminary data, obtained with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I), included in hPL, revealed that these factors were able to antagonized Sorafenib in a proliferation assay, in particular when used in combination. Platelet factors can antagonize Sorafenib or Regorafenib-mediated growth inhibition and apoptosis in HCC cells. The modulation of platelet activity or numbers has the potential to enhance multikinase drug actions

  7. The human HECA interacts with cyclins and CDKs to antagonize Wnt-mediated proliferation and chemoresistance of head and neck cancer cells

    International Nuclear Information System (INIS)

    There is a growing evidence that the human homologue of the Drosophila headcase (HECA) plays an important role in human carcinogenesis. So far specific protein interaction partners and affected signaling pathways of HECA are still elusive. In a recent study we showed that HECA overexpression in oral squamous-cell carcinoma (OSCC) keratinocytes has tumor suppressive effects resulting in a recuperation of cell cycle control concerning the entry and progression of S-phase, G2- and M-phase. Currently, quantitative RT-PCR and immunohistochemical analysis of primary tumor tissue from OSCC patients demonstrate that HECA expression is markedly decreased compared to normal control patients with abundant HECA expression. Additionally, there is nearly no HECA expression in OSCC metastases. Here, we show that HECA expression is negatively controlled by the Wnt-pathway and TCF4, a Wnt related transcription factor, binds to the HECA promoter. Furthermore, immunocytochemistry reveals colocalization of HECA with the cyclin dependent kinase CDK9. Immunoprecipitation experiments and proximity ligation assays further reveal an interaction of HECA with CDK2, CDK9, Cyclin A and Cyclin K, a direct transcriptional target of the p53 tumor suppressor. Silencing HECA in OSCC cell lines leads to a significant increase of cell division and a markedly increased resistance against the chemotherapeutic cisplatin. On the contrary, HECA overexpressing OSCC cell lines show decreased resistance of OSCC cells against cisplatin. Therefore, HECA could be considered as future therapeutic agent against Wnt-dependent tumor progression. -- Highlights: ► HECA is a new cell cycle regulator with anti-tumor features in head and neck cancer. ► During tumor progression HECA mRNA and protein expression decrease. ► The HECA promotor is a direct target of the Wnt/beta-catenin/TCF-pathway. ► The HECA protein antagonizes Wnt-mediated cell proliferation through interaction with major cell cycle factors.

  8. Three distinct suppressors of RNA silencing encoded by a 20-kb viral RNA genome

    Science.gov (United States)

    Lu, Rui; Folimonov, Alexey; Shintaku, Michael; Li, Wan-Xiang; Falk, Bryce W.; Dawson, William O.; Ding, Shou-Wei

    2004-11-01

    Viral infection in both plant and invertebrate hosts requires a virus-encoded function to block the RNA silencing antiviral defense. Here, we report the identification and characterization of three distinct suppressors of RNA silencing encoded by the 20-kb plus-strand RNA genome of citrus tristeza virus (CTV). When introduced by genetic crosses into plants carrying a silencing transgene, both p20 and p23, but not coat protein (CP), restored expression of the transgene. Although none of the CTV proteins prevented DNA methylation of the transgene, export of the silencing signal (capable of mediating intercellular silencing spread) was detected only from the F1 plants expressing p23 and not from the CP- or p20-expressing F1 plants, demonstrating suppression of intercellular silencing by CP and p20 but not by p23. Thus, intracellular and intercellular silencing are each targeted by a CTV protein, whereas the third, p20, inhibits silencing at both levels. Notably, CP suppresses intercellular silencing without interfering with intracellular silencing. The novel property of CP suggests a mechanism distinct to p20 and all of the other viral suppressors known to interfere with intercellular silencing and that this class of viral suppressors may not be consistently identified by Agrobacterium coinfiltration because it also induces RNA silencing against the infiltrated suppressor transgene. Our analyses reveal a sophisticated viral counter-defense strategy that targets the silencing antiviral pathway at multiple steps and may be essential for protecting CTV with such a large RNA genome from antiviral silencing in the perennial tree host. RNA interference | citrus tristeza virus | virus synergy | antiviral immunity

  9. Attachment issues: kinetochore transformations and spindle checkpoint silencing.

    Science.gov (United States)

    Etemad, Banafsheh; Kops, Geert J P L

    2016-04-01

    Cell division culminates in the segregation of duplicated chromosomes in opposite directions prior to cellular fission. This process is guarded by the spindle assembly checkpoint (SAC), which prevents the anaphase of cell division until stable connections between spindle microtubules and the kinetochores of all chromosomes are established. The anaphase inhibitor is generated at unattached kinetochores and inhibitor production is prevented when microtubules are captured. Understanding the molecular changes in the kinetochore that are evoked by microtubule attachments is crucial for understanding the mechanisms of SAC signaling and silencing. Here, we highlight the most recent findings on these events, pinpoint some remaining mysteries, and argue for incorporating holistic views of kinetochore dynamics in order to understand SAC silencing. PMID:26947988

  10. Bacterial Cellular Engineering by Genome Editing and Gene Silencing

    Directory of Open Access Journals (Sweden)

    Nobutaka Nakashima

    2014-02-01

    Full Text Available Genome editing is an important technology for bacterial cellular engineering, which is commonly conducted by homologous recombination-based procedures, including gene knockout (disruption, knock-in (insertion, and allelic exchange. In addition, some new recombination-independent approaches have emerged that utilize catalytic RNAs, artificial nucleases, nucleic acid analogs, and peptide nucleic acids. Apart from these methods, which directly modify the genomic structure, an alternative approach is to conditionally modify the gene expression profile at the posttranscriptional level without altering the genomes. This is performed by expressing antisense RNAs to knock down (silence target mRNAs in vivo. This review describes the features and recent advances on methods used in genomic engineering and silencing technologies that are advantageously used for bacterial cellular engineering.

  11. The weight of the word: knowing silences in obesity research.

    Science.gov (United States)

    Warin, Megan J; Gunson, Jessica S

    2013-12-01

    In this article, we examine the ethical and methodological tensions entailed in doing qualitative research in obesity studies. Framing our own embodied engagements through critical social theory, we consider how cultural meanings associated with obesity are silenced and negotiated in the research process. This negotiation is fraught with linguistic and corporeal challenges, beginning with the decision to use (or not use) the word obesity in research materials. Obesity is a visible stigma, and we argue that silencing language does not erase the tacit judgments that accompany discursive categorization. It is in a broader context of power relations that we examine the relationship between researcher and participant bodies and the ways in which collective knowingness about fat bodies underpins methodological engagement. The simultaneous presence and absence of obesity have a significant impact on the research process, in shaping both participants' experiences and the researcher's actions and interpretations. PMID:24159004

  12. Silences and moral narratives: infanticide as reproductive disruption.

    Science.gov (United States)

    Aengst, Jennifer

    2014-01-01

    Infanticide is a widespread practice, yet few ethnographic and theoretical works examine this. Drawing on ethnographic research conducted in the Indian Himalayas, I argue that infanticide is a form of reproductive disruption that elicits both public moral judgments and private silences. In this Himalayan context, the stigmas of abortion and premarital sex prevent community acknowledgement of infanticide and baby abandonment. Unmarried women hide their pregnancies, deliver and abandon their babies, and later are rushed to the hospital with postdelivery complications. While biomedical doctors deal with the debris of infanticide (postpartum hemorrhage), there is no formal accounting of the practice. I argue that by regarding infanticide as a form of reproductive disruption, we can open up women's narratives of pain and suffering that are silenced because of moral repugnance. PMID:24321033

  13. Els pedagògics sons dels silencis. Enllà del silenci d’Auschwitz Los pedagógicos sonidos de los silencios. Más allá del silencio de Auschwitz The pedagogical sounds of silences. Beyond the silence of Auschwitz

    Directory of Open Access Journals (Sweden)

    Marta Burguet Arfelis

    2009-01-01

    Full Text Available Després del gran silenci d’Auschwitz, en aquest passeig pedagògic descriptiu pels sons dels silencis, ens introduïm en les semàntiques dels silencis, acceptant la seva polisèmia i descrivintne algunes de les accepcions més vinculades a l’àmbit educatiu. S’analitza, d’una banda, la genealogia dels silencis, algunes de les seves claus d’origen, i de l’altra, la teleologia dels silencis, la finalitat, pedagògica o no, dels mateixos. Alhora, partint del silenci com a valor pedagògic en aquesta educació al llarg de tota la vida, es proposen cinc etapes progressives per treballar pedagògicament els silencis, tot apostant per un salt qualitatiu axiològic entre el silenci com a estadi –estar en silenci– i el silenci com a seïtat –ser silenci–. _____________________________________________ Après le grand silence d’Auschwitz, dans ce passage de pédagogie descriptive par les sons des silences, nous nous introduisons dans les sémantiques des silences, en acceptant leur polysémie et en en décrivant certaines acceptions parmi les plus étroitement liées au domaine éducatif. Nous analysons, d’une part, la généalogie des silences, certaines de leur clés d’origine et, de l’autre, la téléologie des silences, et leur finalité, pédagogique ou non. Parallèlement, en partant du silence en tant que valeur pédagogique dans cette éducation tout au long de la vie, nous proposons cinq étapes progressives dans lesquelles travailler pédagogiquement les silences, tout en faisant le pari d’un saut qualitatif axiologique entre le silence en tant qu’état —demeurer en silence— et le silence en tant que manière d’être —être silencieux.Después del gran silencio de Auschwitz, en este paseo pedagógico descriptivo por los sonidos de los silencios nos introducimos en las semánticas de los silencios, aceptando su polisemia i describiendo algunas de las acepciones más vinculadas al ámbito educativo. Se

  14. The effects of thinking in silence on creativity and innovation

    OpenAIRE

    de Vet, A.J.

    2007-01-01

    This dissertation consists of three empirical studies on the effects of thinking in silence on creativity and innovation. In these studies I use a social psychology and cognitive psychology lens to study creativity and innovation at the individual and at the team level of analysis, using randomized experiments to test hypothesized causal relationships. In the first study I find that when the ability to modify self-presentation is low and the sensitivity to expressive behavior of others is hig...

  15. Hearing the Silence: Children’s Voices on Violence

    OpenAIRE

    Collins, Kathryn S.

    2003-01-01

    Each year more than five million children in the United States are exposed to traumatizing events in their communities. This paper presents a discussion of multiple areas in violence and victimization research that needs to be continued as well as provides suggestions on how to un-silence child survivors through bridging the gaps between research and practice. It reviews the overarching problem of violence in the U.S. at the domestic and global levels and the effects of victimi...

  16. Epigenetic silencing of CYP24 in the tumor microenvironment

    OpenAIRE

    Johnson, Candace S.; Chung, Ivy; Trump, Donald L.

    2010-01-01

    Calcitriol (1,25 dihydroxycholecalciferol) has significant antitumor activity in vitro and in vivo in a number of tumor model systems. We developed a system for isolation of fresh endothelial cells from tumors and Matrigel environments which demonstrate that CYP24, the catabolic enzyme involved in vitamin D signaling, is epigenetically silenced selectively in tumor-derived endothelial cells (TDEC). TDEC maintain phenotypic characteristics which are distinct from endothelial cells isolated fro...

  17. Relationships between Voice, Silence and Identity formation in organizations

    OpenAIRE

    Horia MOAŞA

    2012-01-01

    Language and voice are very important in the formation of identity, but if that very language/ voice is absent because of censorship, silencing or lack of voice, limited discursive or symbolic resources, how are individuals going to construct their identity? On the one hand, the challenge of identity is to incorporate multiple and diverse elements in order to build a sense of self-continuity and coherence. On the other hand, multiple and diverse moments and contexts offer people the possibili...

  18. LNA-antisense rivals siRNA for gene silencing

    DEFF Research Database (Denmark)

    Jepsen, Jan Stenvang; Wengel, Jesper; Stenvang, Jan

    2004-01-01

    Locked nucleic acid (LNA) is a class of nucleic acid analogs possessing unprecedented binding affinity toward complementary DNA and RNA while obeying the Watson-Crick base-pairing rules. For efficient gene silencing in vitro and in vivo, fully modified or chimeric LNA oligonucleotides have been...... phosphorothioate-DNA segment flanked by LNA gaps, rivals siRNA as the technology of choice for target validation and therapeutic applications....

  19. Optical silencing of C. elegans cells with arch proton pump.

    Directory of Open Access Journals (Sweden)

    Ayako Okazaki

    Full Text Available BACKGROUND: Optogenetic techniques using light-driven ion channels or ion pumps for controlling excitable cells have greatly facilitated the investigation of nervous systems in vivo. A model organism, C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. METHODOLOGY/PRINCIPAL FINDINGS: We describe the application of archaerhodopsin-3 (Arch, a recently reported optical neuronal silencer, to C. elegans. Arch::GFP expressed either in all neurons or body wall muscles of the entire body by means of transgenes were localized, at least partially, to the cell membrane without adverse effects, and caused locomotory paralysis of worms when illuminated by green light (550 nm. Pan-neuronal expression of Arch endowed worms with quick and sustained responsiveness to such light. Worms reliably responded to repeated periods of illumination and non-illumination, and remained paralyzed under continuous illumination for 30 seconds. Worms expressing Arch in different subsets of motor neurons exhibited distinct defects in the locomotory behavior under green light: selective silencing of A-type motor neurons affected backward movement while silencing of B-type motor neurons affected forward movement more severely. Our experiments using a heat-shock-mediated induction system also indicate that Arch becomes fully functional only 12 hours after induction and remains functional for more than 24 hour. CONCLUSIONS/SGNIFICANCE: Arch can be used for silencing neurons and muscles, and may be a useful alternative to currently widely used halorhodopsin (NpHR in optogenetic studies of C. elegans.

  20. Virus-induced Gene Silencing in Eggplant (Solanum melongena)

    Institute of Scientific and Technical Information of China (English)

    HaipingLiu; Daqi Fu; Benzhong Zhu; Huaxue Yan; Xiaoying Shen; Jinhua Zuo; Yi Zhu; Yunbo Luo

    2012-01-01

    Eggplant (Solanum melongena) is an economically important vegetable requiring investigation into its various genomic functions.The current limitation in the investigation of genomic function in eggplant is the lack of effective tools available for conducting functional assays.Virus-induced gene silencing (VIGS) has played a critical role in the functional genetic analyses.In this paper,TRV-mediated VIGS was successfully elicited in eggplant.We first cloned the CDS sequence of PDS (PHYTOENE DESATURASE) in eggplant and then silenced the PDS gene.Photo-bleaching was shown on the newly-developed leaves four weeks after agroinoculation,indicating that VIGS can be used to silence genes in eggplant.To further illustrate the reliability of VIGS in eggplant,we selected Chl H,Su and CLA1 as reporters to elicit VIGS using the high-pressure spray method.Suppression of Chl H and Su led to yellow leaves,while the depletion of CLA1 resulted in albino.In conclusion,four genes,PDS,Chl H,Su (Sulfur),CLA1,were down-regulated significantly by VIGS,indicating that the VIGS system can be successfully applied in eggplant and is a reliable tool for the study of gene function.

  1. Epigenetic silencing of tumor suppressor genes: Paradigms, puzzles, and potential.

    Science.gov (United States)

    Kazanets, Anna; Shorstova, Tatiana; Hilmi, Khalid; Marques, Maud; Witcher, Michael

    2016-04-01

    Cancer constitutes a set of diseases with heterogeneous molecular pathologies. However, there are a number of universal aberrations common to all cancers, one of these being the epigenetic silencing of tumor suppressor genes (TSGs). The silencing of TSGs is thought to be an early, driving event in the oncogenic process. With this in consideration, great efforts have been made to develop small molecules aimed at the restoration of TSGs in order to limit tumor cell proliferation and survival. However, the molecular forces that drive the broad epigenetic reprogramming and transcriptional repression of these genes remain ill-defined. Undoubtedly, understanding the molecular underpinnings of transcriptionally silenced TSGs will aid us in our ability to reactivate these key anti-cancer targets. Here, we describe what we consider to be the five most logical molecular mechanisms that may account for this widely observed phenomenon: 1) ablation of transcription factor binding, 2) overexpression of DNA methyltransferases, 3) disruption of CTCF binding, 4) elevation of EZH2 activity, 5) aberrant expression of long non-coding RNAs. The strengths and weaknesses of each proposed mechanism is highlighted, followed by an overview of clinical efforts to target these processes. PMID:27085853

  2. Epigenetic silencing of CYP24 in the tumor microenvironment

    Science.gov (United States)

    Johnson, Candace S.; Chung, Ivy; Trump, Donald L.

    2010-01-01

    Calcitriol (1,25 dihydroxycholecalciferol) has significant antitumor activity in vitro and in vivo in a number of tumor model systems. We developed a system for isolation of fresh endothelial cells from tumors and Matrigel environments which demonstrate that CYP24, the catabolic enzyme involved in vitamin D signaling, is epigenetically silenced selectively in tumor-derived endothelial cells (TDEC). TDEC maintain phenotypic characteristics which are distinct from endothelial cells isolated from normal tissues and from Matrigel plugs (MDEC). In TDEC, calcitriol induces G0/G1 arrest, modulates p27 and p21, and induces apoptotic cell death and decreases P-Erk and P-Akt. In contrast, endothelial cells isolated from normal tissues and MDEC are unresponsive to calcitriol-mediated anti-proliferative effects despite intact signaling through the vitamin D receptor (VDR). In TDEC, which is sensitive to calcitriol, the CYP24 promoter is hypermethylated in two CpG island regions located at the 5′end; this hypermethylation may contribute to gene silencing of CYP24. The extent of methylation in these two regions is significantly less in MDEC. Lastly, treatment of TDEC with a DNA methyltransferase inhibitor restores calcitriol-mediated induction of CYP24 and resistance to calcitriol. These data suggest that epigenetic silencing of CYP24 modulates cellular responses to calcitriol. PMID:20304059

  3. Right to Silence%沉默权论要

    Institute of Scientific and Technical Information of China (English)

    朱华

    2012-01-01

    Right to silence in the criminal procedure law is a human rights protection system that can basically make a balance between the public authority of the State and the right to freedom of statement of suspects and defendants.Dealing well with the relationship between the right to silence and the right of questioning can help to improve objectivity and accuracy of criminal cases and reduce trumped-up cases caused by torture.The relative implied right to silence is the result of the development of modern civilization and the rule of law,and conforms to China's basic national condition and current status.%刑事诉讼法中的沉默权,是国家公权力与嫌疑人、被告人陈述自由权得到基本平衡的人权保障制度。处理好沉默权与讯问权的关系,有利于提高刑事案件的客观性和准确性,减少因刑讯逼供产生的冤假错案,默示的相对沉默权,是现代文明法治发展的结果,符合我国基本国情及现状。

  4. Epigenetic silencers are enriched in dormant desert frog muscle.

    Science.gov (United States)

    Hudson, Nicholas J; Lonhienne, T G A; Franklin, Craig E; Harper, Gregory S; Lehnert, S A

    2008-08-01

    Green-striped burrowing frogs, Cyclorana alboguttata, survive droughts by entering a metabolic depression called aestivation, characterised by a reduction in resting oxygen consumption by 80%. Aestivation in C. alboguttata is manifest by transcriptional silencing of skeletal muscle bioenergetic genes, such as NADH ubiquinone oxidoreductase 1, ATP synthase and superoxide dismutase 2. In this study, we hypothesised that aestivation is associated with epigenetic change in frog muscle. We assessed mRNA transcript abundance of seven genes that code for proteins with established roles in epigenetically-mediated gene silencing [transcriptional co-repressor SIN3A, DNA (cytosine-5-) methyltransferase 1, methyl CpG binding protein 2, chromodomain helicase DNA binding protein 4, histone binding protein rbbp4, histone deacetylase 1 and nuclear receptor co-repressor 2] using qRT-PCR. These seven genes showed a modest (1.1-3.5-fold) but coordinated upregulation in 6-month aestivating muscle. This reached significance for SIN3A and DNA cytosine-5-methyltransferase 1 in standard pair-wise comparisons (p < 0.05), and the candidates as a whole when analysed by Fisher's combined probability test (p < 0.01). These data are consistent with the hypothesis that the transcriptional silencing and metabolic depression that occurs during seasonal dormancy are associated with chromatin remodelling, and present a novel example of an environmentally induced epigenetic modification in an adult vertebrate. PMID:18369641

  5. Silencing Deafness: Displacing Disability in the Nineteenth Century

    Directory of Open Access Journals (Sweden)

    Esme Cleall

    2015-03-01

    Full Text Available This article traces the way in which the language of displacement and silence were used in nineteenth-century discussions of deafness and connects this tendency to the marginalised place deaf experience occupies historically. Throughout the nineteenth century, a period which saw the consolidation of ‘the deaf and dumb’ as a social category, the word ‘forgetting’ crept into numerous discussions of deafness by both deaf and hearing commentators. Some, such as the educationalist Alexander Graeme Bell, were overt in their desire to forget deafness, demanding disability was ‘bred out’ and deaf culture condemned to the forgotten past. Others used the term ambivalently and sometimes metaphorically discussing the deaf as ‘forgotten’ by society, and ‘children of silence’. Some even pleaded that people who were deaf were not forgotten. But, though varied, the use of the imagery of forgetting and silence to evoke deafness is recurrent, and may, therefore, be seen to reveal something about how deaf experience can be approached as a displacement where deafness was spatially and imaginatively marginalised. I argue that one of the consequences of the conceptual framing of deafness through the language of forgetting was actively to silence deafness and to neutralise the idea that disability should be marginal and could be forgotten.

  6. Aureusvirus P14 Is an Efficient RNA Silencing Suppressor That Binds Double-Stranded RNAs without Size Specificity‡

    OpenAIRE

    Mérai, Zsuzsanna; Kerényi, Zoltán; Molnár, Attila; Barta, Endre; Válóczi, Anna; Bisztray, György; Havelda, Zoltán; Burgyán, József; Silhavy, Dániel

    2005-01-01

    RNA silencing is a conserved eukaryotic gene regulatory system in which sequence specificity is determined by small RNAs. Plant RNA silencing also acts as an antiviral mechanism; therefore, viral infection requires expression of a silencing suppressor. The mechanism and the evolution of silencing suppression are still poorly understood. Tombusvirus open reading frame (ORF) 5-encoded P19 is a size-selective double-stranded RNA (dsRNA) binding protein that suppresses silencing by sequestering d...

  7. Rescue of Mtp siRNA-induced hepatic steatosis by DGAT2 siRNA silencing[S

    OpenAIRE

    Tep, Samnang; Mihaila, Radu; Freeman, Alexander; Pickering, Victoria; Huynh, Felicia; Tadin-Strapps, Marija; Stracks, Allison; Hubbard, Brian; Caldwell, Jeremy; Flanagan, W. Michael; Kuklin, Nelly A.; Ason, Brandon

    2012-01-01

    Microsomal triglyceride transfer protein (Mtp) inhibitors represent a novel therapeutic approach to lower circulating LDL cholesterol, although therapeutic development has been hindered by the observed increase in hepatic triglycerides and liver steatosis following treatment. Here, we used small interfering RNAs (siRNA) targeting Mtp to achieve target-specific silencing to study this phenomenon and to determine to what extent liver steatosis is induced by changes in Mtp expression. We observe...

  8. DICER-LIKE2 plays a primary role in transitive silencing of transgenes in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Sizolwenkosi Mlotshwa

    Full Text Available Dicer-like (DCL enzymes play a pivotal role in RNA silencing in plants, processing the long double-stranded RNA (dsRNA that triggers silencing into the primary short interfering RNAs (siRNAs that mediate it. The siRNA population can be augmented and silencing amplified via transitivity, an RNA-dependent RNA polymerase (RDR-dependent pathway that uses the target RNA as substrate to generate secondary siRNAs. Here we report that Arabidopsis DCL2-but not DCL4-is required for transitivity in cell-autonomous, post-transcriptional silencing of transgenes. An insertion mutation in DCL2 blocked sense transgene-induced silencing and eliminated accumulation of the associated RDR-dependent siRNAs. In hairpin transgene-induced silencing, the dcl2 mutation likewise eliminated accumulation of secondary siRNAs and blocked transitive silencing, but did not block silencing mediated by primary siRNAs. Strikingly, in all cases, the dcl2 mutation eliminated accumulation of all secondary siRNAs, including those generated by other DCL enzymes. In contrast, mutations in DCL4 promoted a dramatic shift to transitive silencing in the case of the hairpin transgene and enhanced silencing induced by the sense transgene. Suppression of hairpin and sense transgene silencing by the P1/HC-Pro and P38 viral suppressors was associated with elimination of secondary siRNA accumulation, but the suppressors did not block processing of the stem of the hairpin transcript into primary siRNAs. Thus, these viral suppressors resemble the dcl2 mutation in their effects on siRNA biogenesis. We conclude that DCL2 plays an essential, as opposed to redundant, role in transitive silencing of transgenes and may play a more important role in silencing of viruses than currently thought.

  9. Suffering in silence: Investigating the role of fear in the relationship between abusive supervision and defensive silence.

    Science.gov (United States)

    Kiewitz, Christian; Restubog, Simon Lloyd D; Shoss, Mindy K; Garcia, Patrick Raymund James M; Tang, Robert L

    2016-05-01

    Drawing from an approach-avoidance perspective, we examine the relationships between subordinates' perceptions of abusive supervision, fear, defensive silence, and ultimately abusive supervision at a later time point. We also account for the effects of subordinates' assertiveness and individual perceptions of a climate of fear on these predicted mediated relationships. We test this moderated mediation model with data from three studies involving different sources collected across various measurement periods. Results corroborated our predictions by showing (a) a significant association between abusive supervision and subordinates' fear, (b) second-stage moderation effects of subordinates' assertiveness and their individual perceptions of a climate of fear in the abusive supervision-fear-defensive silence relationship (with lower assertiveness and higher levels of climate-of-fear perceptions exacerbating the detrimental effects of fear resulting from abusive supervision), and (c) first-stage moderation effects of subordinates' assertiveness and climate-of-fear perceptions in a model linking fear to defensive silence and abusive supervision at a later time. Theoretical and practical implications are discussed. (PsycINFO Database Record PMID:26727209

  10. Technical advances in trigger-induced RNA interference gene silencing in the parasite Entamoeba histolytica.

    Science.gov (United States)

    Khalil, Mohamed I; Foda, Bardees M; Suresh, Susmitha; Singh, Upinder

    2016-03-01

    Entamoeba histolytica has a robust endogenous RNA interference (RNAi) pathway. There are abundant 27 nucleotide (nt) anti-sense small RNAs (AS sRNAs) that target genes for silencing and the genome encodes many genes involved in the RNAi pathway such as Argonaute proteins. Importantly, an E. histolytica gene with numerous AS sRNAs can function as a "trigger" to induce silencing of a gene that is fused to the trigger. Thus, the amebic RNAi pathway regulates gene expression relevant to amebic biology and has additionally been harnessed as a tool for genetic manipulation. In this study we have further improved the trigger-induced gene silencing method. We demonstrate that rather than using the full-length gene, a short portion of the coding region fused to a trigger is sufficient to induce silencing; the first 537 bp of the E. histolytica rhomboid gene (EhROM1) fused in-frame to the trigger was sufficient to silence EhROM1. We also demonstrated that the trigger method could silence two amebic genes concomitantly; fusion of the coding regions of EhROM1 and transcription factor, EhMyb, in-frame to a trigger gene resulted in both genes being silenced. Alternatively, two genes can be silenced sequentially: EhROM1-silenced parasites with no drug selection plasmid were transfected with trigger-EhMyb, resulting in parasites with both EhROM1 and EhMyb silenced. With all approaches tested, the trigger-mediated silencing was substantive and silencing was maintained despite loss of the G418 selectable marker. All gene silencing was associated with generation of AS sRNAs to the silenced gene. We tested the reversibility of the trigger system using inhibitors of histone modifications but found that the silencing was highly stable. This work represents a technical advance in the trigger gene silencing method in E. histolytica. Approaches that readily silence multiple genes add significantly to the genetic toolkit available to the ameba research community. PMID:26747561

  11. Application of the operational model of agonism to establish conditions when functional antagonism may be used to estimate agonist dissociation constants.

    OpenAIRE

    Leff, P.; Martin, G R; Morse, J. M.

    1985-01-01

    The operational model of agonism (Black & Leff, 1983) has been used to analyse comparatively functional antagonism and irreversible antagonism as methods for estimating agonist dissociation constants (KAs). A general condition is established in terms of the model parameters which defines the type of experimental interventions at the receptor and the post-receptor level that allow valid KA estimation. It is shown that functional antagonism and other post-receptor interventions may produce chan...

  12. Gene silencing: Double-stranded RNA mediated mRNA degradation and gene inactivation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The recent development of gene transfer approaches in plants and animals has revealed that transgene can undergo silencing after integration in the genome. Host genes can also be silenced as a consequence of the presence of a homologous transgene. More and more investigations have demonstrated that doublestranded RNA can silence genes by triggering degradation of homologous RNA in the cytoplasm and by directing methylation of homologous nuclear DNA sequences. Analyses of Arabidopsis mutants and plant viral suppressors of silencing are unraveling RNA-silencing mechanisms and are assessing the role of methylation in transcriptional and posttranscriptional gene silencing. This review will focus on double-stranded RNA mediated mRNA degradation and gene inactivation in plants.

  13. Disruption of Cell-to-Cell Signaling Does Not Abolish the Antagonism of Phaeobacter gallaeciensis toward the Fish Pathogen Vibrio anguillarum in Algal Systems

    DEFF Research Database (Denmark)

    Prol García, María Jesús; D'Alvise, Paul; Gram, Lone

    2013-01-01

    Quorum sensing (QS) regulates Phaeobacter gallaeciensis antagonism in broth systems; however, we demonstrate here that QS is not important for antagonism in algal cultures. QS mutants reduced Vibrio anguillarum to the same extent as the wild type. Consequently, a combination of probiotic Phaeobac......Quorum sensing (QS) regulates Phaeobacter gallaeciensis antagonism in broth systems; however, we demonstrate here that QS is not important for antagonism in algal cultures. QS mutants reduced Vibrio anguillarum to the same extent as the wild type. Consequently, a combination of probiotic...

  14. Plant responses against invasive nucleic acids: RNA silencing and its suppression by plant viral pathogens

    OpenAIRE

    Alvarado, Veria; Herman B Scholthof

    2009-01-01

    RNA silencing is a common strategy shared by eukaryotic organisms to regulate gene expression, and also operates as a defense mechanism against invasive nucleic acids such as viral transcripts. The silencing pathway is quite sophisticated in higher eukaryotes but the distinct steps and nature of effector complexes vary between and even within species. To counteract this defense mechanism viruses have evolved the ability to encode proteins that suppress silencing to protect their genomes from ...

  15. Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation

    Directory of Open Access Journals (Sweden)

    Tang Y Amy

    2010-05-01

    Full Text Available Abstract Background X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1 repeats are relatively enriched on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes. Results Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could confer the capacity for relatively efficient chromosome-wide silencing. Conclusions This study provides insight into the requirements for efficient Xist mediated silencing and specifically identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major influence on the ability of Xist-mediated silencing to be propagated in a continuous

  16. Three distinct suppressors of RNA silencing encoded by a 20-kb viral RNA genome

    OpenAIRE

    R. Lu; Folimonov, A; Shintaku, M; Li, W. X.; Falk, B W; Dawson, W O; Ding, S W

    2004-01-01

    Viral infection in both plant and invertebrate hosts requires a virus-encoded function to block the RNA silencing antiviral defense. Here, we report the identification and characterization of three distinct suppressors of RNA silencing encoded by the approximate to20-kb plus-strand RNA genome of citrus tristeza virus (CTV). When introduced by genetic crosses into plants carrying a silencing transgene, both p20 and p23, but not coat protein (CP), restored expression of the transgene. Although ...

  17. Post-transcriptional regulation of meiotic genes by a nuclear RNA silencing complex

    OpenAIRE

    Egan, Emily D.; Braun, Craig R.; Gygi, Steven P.; Moazed, Danesh

    2014-01-01

    The authors define a multiprotein nuclear RNA silencing (NURS) complex that mediates silencing of meiotic genes during vegetative growth in the fission yeast S. pombe. Meiotic gene silencing occurs post-transcriptionally through recruitment of the exosome complex to promote RNA degradation. Extensive interaction analysis and functional characterizations link the NURS complex to specific RNA-binding and processing proteins and also chromatin modification machinery.

  18. High-Performance Genetically Targetable Optical Neural Silencing via Light-Driven Proton Pumps

    OpenAIRE

    Chow, Brian Y.; Han, Xue; Dobry, Allison S.; Qian, Xiaofeng; Chuong, Amy S.; Li, Mingjie; Henninger, Michael A.; Belfort, Gabriel M.; Lin, Yingxi; Monahan, Patrick E; Boyden, Edward S

    2010-01-01

    The ability to silence the activity of genetically specified neurons in a temporally precise fashion would open up the ability to investigate the causal role of specific cell classes in neural computations, behaviors, and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate very powerful, safe, multiple-color silencing of neural activity. The gene archaerhodopsin-31 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the a...

  19. Group II metabotropic glutamate receptor antagonism prevents the antiallodynic effects of R-isovaline.

    Science.gov (United States)

    Asseri, K A; Puil, E; Schwarz, S K W; MacLeod, B A

    2015-05-01

    We previously showed that isovaline is a peripheral analgesic which acts in vivo and in brain slices as an atypical metabotropic GABA(B) agonist. Peripheral inhibitory group II and III metabotropic glutamate receptors (mGluRs) belong to the same family C as GABA(B) receptors; therefore, we hypothesized that isovaline's analgesic effects could include their activation. We examined the effects of R-isovaline on mechanical allodynia produced by prostaglandin E2 in the mouse paw. Subcutaneous R-isovaline produced dose-dependent antiallodynia restricted to the injected hindlimb. This antiallodynia was blocked by co-injection with a selective group II mGluR antagonist, LY341495, but not a group III mGluR antagonist (MAP-4). The antiallodynic effect of R-isovaline was potentiated by co-administration of a group II mGluR-positive allosteric modulator, LY487379. Injection of a group II mGluR agonist (LY354740) produced an antiallodynic effect which was completely reversed by group II antagonism, but was not affected by group III or GABA(B) (CGP35348) antagonism. Similarly, group II mGluR antagonism did not alter the antiallodynia produced by the prototypical GABA(B) agonist, baclofen. Hence, there was no apparent crosstalk between group II mGluRs and GABA(B) receptors. Previous studies have demonstrated that peripheral GABA(B) receptor activation by isovaline produces antiallodynia. In addition, the present results indicate that activation of peripheral group II mGluRs by R-isovaline produces antiallodynia. PMID:25701709

  20. Genomic conflicts and sexual antagonism in human health: insights from oxytocin and testosterone.

    Science.gov (United States)

    Mokkonen, Mikael; Crespi, Bernard J

    2015-04-01

    We review the hypothesized and observed effects of two of the major forms of genomic conflicts, genomic imprinting and sexual antagonism, on human health. We focus on phenotypes mediated by peptide and steroid hormones (especially oxytocin and testosterone) because such hormones centrally mediate patterns of physical and behavioral resource allocation that underlie both forms of conflict. In early development, a suite of imprinted genes modulates the human oxytocinergic system as predicted from theory, with paternally inherited gene expression associated with higher oxytocin production, and increased solicitation to mothers by infants. This system is predicted to impact health through the incompatibility of paternal-gene and maternal-gene optima and increased vulnerability of imprinted gene systems to genetic and epigenetic changes. Early alterations to oxytocinergic systems have long-term negative impacts on human psychological health, especially through their effects on attachment and social behavior. In contrast to genomic imprinting, which generates maladaptation along an axis of mother-infant attachment, sexual antagonism is predicted from theory to generate maladaptation along an axis of sexual dimorphism, modulated by steroid and peptide hormones. We describe evidence of sexual antagonism from studies of humans and other animals, demonstrating that sexually antagonistic effects on sex-dimorphic phenotypes, including aspects of immunity, life history, psychology, and behavior, are commonly observed and lead to forms of maladaptation that are demonstrated, or expected, to impact human health. Recent epidemiological and psychiatric studies of schizophrenia in particular indicate that it is mediated, in part, by sexually antagonistic alleles. The primary implication of this review is that data collection focused on (i) effects of imprinted genes that modulate the oxytocin system, and (ii) effects of sexually antagonistic alleles on sex-dimorphic, disease

  1. Sexual antagonism and meiotic drive cause stable linkage disequilibrium and favour reduced recombination on the X chromosome.

    Science.gov (United States)

    Rydzewski, W T; Carioscia, S A; Liévano, G; Lynch, V D; Patten, M M

    2016-06-01

    Sexual antagonism and meiotic drive are sex-specific evolutionary forces with the potential to shape genomic architecture. Previous theory has found that pairing two sexually antagonistic loci or combining sexual antagonism with meiotic drive at linked autosomal loci augments genetic variation, produces stable linkage disequilibrium (LD) and favours reduced recombination. However, the influence of these two forces has not been examined on the X chromosome, which is thought to be enriched for sexual antagonism and meiotic drive. We investigate the evolution of the X chromosome under both sexual antagonism and meiotic drive with two models: in one, both loci experience sexual antagonism; in the other, we pair a meiotic drive locus with a sexually antagonistic locus. We find that LD arises between the two loci in both models, even when the two loci freely recombine in females and that driving haplotypes will be enriched for male-beneficial alleles, further skewing sex ratios in these populations. We introduce a new measure of LD, Dz', which accounts for population allele frequencies and is appropriate for instances where these are sex specific. Both models demonstrate that natural selection favours modifiers that reduce the recombination rate. These results inform observed patterns of congealment found on driving X chromosomes and have implications for patterns of natural variation and the evolution of recombination rates on the X chromosome. PMID:26999777

  2. Orexin-1 receptor blockade dysregulates REM sleep in the presence of orexin-2 receptor antagonism

    OpenAIRE

    Christine eDugovic; Shelton, Jonathan E.; Sujin eYun; Pascal eBonaventure; Shireman, Brock T.; Lovenberg, Timothy W.

    2014-01-01

    In accordance with the prominent role of orexins in the maintenance of wakefulness via activation of orexin-1 (OX1R) and orexin-2 (OX2R) receptors, various dual OX1/2R antagonists have been shown to promote sleep in animals and humans. While selective blockade of OX2R seems to be sufficient to initiate and prolong sleep, the beneficial effect of additional inhibition of OX1R remains controversial. The relative contribution of OX1R and OX2R to the sleep effects induced by a dual OX1/2R antagon...

  3. Antagonism of peptidoleukotrienes and inhibition of systemic anaphylaxis by RG 12525 in guinea pigs

    International Nuclear Information System (INIS)

    RG 12525 was determined to be a specific, competitive and orally effective antagonist of the peptidoleukotrienes, LTC4, LTD4 and LTE4, in several assays utilizing guinea pigs. In vitro, RG 12525 competitively inhibited 3H-LTD4 binding to lung membranes and competitively antagonized the spasmogenic activity of LTC4, LTD4 and LTE4 on lung strips with > 8000 fold selectivity. In vivo, RG 12525 orally inhibited LTD4 induced wheal formation LTD4 induced bronchoconstriction and anaphylactic death and antigen induced bronchoconstriction. RG 12525 represents a significant improvement in receptor affinity and oral efficacy and thus, is a valuable pharmacological tool to evaluate peptidoleukotrienes in allergic diseases

  4. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis

    OpenAIRE

    Rayner, Katey J.; Sheedy, Frederick J.; Esau, Christine C.; Hussain, Farah N.; Temel, Ryan E.; Parathath, Saj; van Gils, Janine M.; Rayner, Alistair J; Chang, Aaron N; Suarez, Yajaira; Fernandez-Hernando, Carlos; Fisher, Edward A.; Moore, Kathryn J.

    2011-01-01

    Plasma HDL levels have a protective role in atherosclerosis, yet clinical therapies to raise HDL levels have remained elusive. Recent advances in the understanding of lipid metabolism have revealed that miR-33, an intronic microRNA located within the SREBF2 gene, suppresses expression of the cholesterol transporter ABC transporter A1 (ABCA1) and lowers HDL levels. Conversely, mechanisms that inhibit miR-33 increase ABCA1 and circulating HDL levels, suggesting that antagonism of miR-33 may be ...

  5. Essential and overlapping functions for mammalian Argonautes in microRNA silencing

    OpenAIRE

    Su, Hong; Trombly, Melanie I.; Chen, Jian; Wang, Xiaozhong

    2009-01-01

    MicroRNA (miRNA) silencing fine-tunes protein output and regulates diverse biological processes. Argonaute (Ago) proteins are the core effectors of the miRNA pathway. In lower organisms, multiple Agos have evolved specialized functions for distinct RNA silencing pathways. However, the roles of mammalian Agos have not been well characterized. Here we show that mouse embryonic stem (ES) cells deficient for Ago1–4 are completely defective in miRNA silencing and undergo apoptosis. In miRNA silenc...

  6. Influence of viral genes on the cell-to-cell spread of RNA silencing

    OpenAIRE

    Zhou, Yu; Ryabov, Eugene; Zhang, Xuemei; Hong, Yiguo

    2008-01-01

    The turnip crinkle virus-based vector TCV–GFPΔCP had been devised previously to study cell-to-cell and long-distance spread of virus-induced RNA silencing. TCV–GFPΔCP, which had been constructed by replacing the coat protein (CP) gene with a green fluorescent protein (GFP) coding sequence, was able to induce RNA silencing in single epidermal cells, from which RNA silencing spread from cell-to-cell. Using this unique local silencing assay together with mutagenesis analysis, two TCV genes, p8 a...

  7. Widespread siRNA “off-target” transcript silencing mediated by seed region sequence complementarity

    OpenAIRE

    Jackson, Aimee L.; Burchard, Julja; Schelter, Janell; Chau, B. Nelson; Cleary, Michele; Lim, Lee; Linsley, Peter S

    2006-01-01

    Transfected siRNAs and miRNAs regulate numerous transcripts that have only limited complementarity to the active strand of the RNA duplex. This process reflects natural target regulation by miRNAs, but is an unintended (“off-target”) consequence of siRNA-mediated silencing. Here we demonstrate that this unintended off-target silencing is widespread, and occurs in a manner reminiscent of target silencing by miRNAs. A high proportion of unintended transcripts silenced by siRNAs showed 3' UTR se...

  8. SAS4 and SAS5 are locus-specific regulators of silencing in Saccharomyces cerevisiae.

    OpenAIRE

    Xu, E Y; S. Kim; Rivier, D H

    1999-01-01

    Sir2p, Sir3p, Sir4p, and the core histones form a repressive chromatin structure that silences transcription in the regions near telomeres and at the HML and HMR cryptic mating-type loci in Saccharomyces cerevisiae. Null alleles of SAS4 and SAS5 suppress silencing defects at HMR; therefore, SAS4 and SAS5 are negative regulators of silencing at HMR. This study revealed that SAS4 and SAS5 contribute to silencing at HML and the telomeres, indicating that SAS4 and SAS5 are positive regulators of ...

  9. Exon silencing by UAGG motifs in response to neuronal excitation.

    Directory of Open Access Journals (Sweden)

    Ping An

    2007-02-01

    Full Text Available Alternative pre-mRNA splicing plays fundamental roles in neurons by generating functional diversity in proteins associated with the communication and connectivity of the synapse. The CI cassette of the NMDA R1 receptor is one of a variety of exons that show an increase in exon skipping in response to cell excitation, but the molecular nature of this splicing responsiveness is not yet understood. Here we investigate the molecular basis for the induced changes in splicing of the CI cassette exon in primary rat cortical cultures in response to KCl-induced depolarization using an expression assay with a tight neuron-specific readout. In this system, exon silencing in response to neuronal excitation was mediated by multiple UAGG-type silencing motifs, and transfer of the motifs to a constitutive exon conferred a similar responsiveness by gain of function. Biochemical analysis of protein binding to UAGG motifs in extracts prepared from treated and mock-treated cortical cultures showed an increase in nuclear hnRNP A1-RNA binding activity in parallel with excitation. Evidence for the role of the NMDA receptor and calcium signaling in the induced splicing response was shown by the use of specific antagonists, as well as cell-permeable inhibitors of signaling pathways. Finally, a wider role for exon-skipping responsiveness is shown to involve additional exons with UAGG-related silencing motifs, and transcripts involved in synaptic functions. These results suggest that, at the post-transcriptional level, excitable exons such as the CI cassette may be involved in strategies by which neurons mount adaptive responses to hyperstimulation.

  10. Sounds of silence%沉默的声音

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Four monks decided to meditate1 silently without speaking for two weeks. By nightfall on the first day,the candle began to flicker and then went out.The first monk said,"Oh, no!The candle is out."The second monk said,"Aren't we not supposed to talk?"The third monk said, "Why must you two break the silence?"The fourth monk laughed and said, "Ha! I'm the only one who didn't speak."

  11. Silencing by imprinted noncoding RNAs: is transcription the answer?

    OpenAIRE

    Pauler, Florian M; Koerner, Martha V.; Barlow, Denise P.

    2007-01-01

    Non-coding RNAs (ncRNAs) with gene regulatory functions are starting to be seen as a common feature of mammalian gene regulation with the discovery that most of the transcriptome is ncRNA. The prototype has long been the Xist ncRNA, which induces X-chromosome inactivation in female cells. However, a new paradigm is emerging – the silencing of imprinted gene clusters by long ncRNAs. Here, we review models by which imprinted ncRNAs could function. We argue that an Xist-like model is only one of...

  12. C Implementation & comparison of companding & silence audio compression techniques

    CERN Document Server

    Dangarwala, Kruti

    2010-01-01

    Just about all the newest living room audio-video electronics and PC multimedia products being designed today will incorporate some form of compressed digitized-audio processing capability. Audio compression reduces the bit rate required to represent an analog audio signal while maintaining the perceived audio quality. Discarding inaudible data reduces the storage, transmission and compute requirements of handling high-quality audio files. This paper covers wave audio file format & algorithm of silence compression method and companding method to compress and decompress wave audio file. Then it compares the result of these two methods.

  13. Sibling violence silenced: rivalry, competition, wrestling, playing, roughhousing, benign.

    Science.gov (United States)

    Phillips, Debby A; Phillips, Kate H; Grupp, Kitty; Trigg, Lisa J

    2009-01-01

    In this article, sibling violence and the silence surrounding it is explicated through professional literature and research findings, exemplars from clinical practice, and statistics. Theoretical positions and discourse analysis have been used to help explain how regular broken bones, bruises, lacerations, and verbal humiliation can be minimized as normal sibling rivalry or roughhousing, which does not cause serious consequences. Nursing should be on the front lines of ending practices of violence. Recognizing sibling violence as such is part of this work and is a social justice issue. PMID:19461218

  14. CAPN5 gene silencing by short hairpin RNA interference

    OpenAIRE

    Nelson, Nnamdi G; Jessica M Skeie; Muradov, Hakim; Rowell, Hannah A; Seo, Seongjin; Mahajan, Vinit B

    2014-01-01

    Background The purpose of this project was to identify short hairpin RNA (shRNA) sequences that can suppress expression of human CAPN5 in which gain-of-function mutants cause autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV). We created HEK293T cells that stably express an ADNIV disease allele, CAPN5-p.R243L. Transfection protocols were optimized for neuroblastoma SHSY5Y cells. The gene silencing effect of four different shRNA plasmids that target CAPN5 was tested. RNA and...

  15. JMJ14, a JmjC domain protein, is required for RNA silencing and cell-to-cell movement of an RNA silencing signal in Arabidopsis

    OpenAIRE

    Searle, I.R.; Melnyk, C. W.; Baulcombe, D. C.; Smith, L. M.; Pontes, O.

    2010-01-01

    JMJ14 is a histone H3 Lys4 (H3K4) trimethyl demethylase that affects mobile RNA silencing in an Arabidopsis transgene system. It also influences CHH DNA methylation, abundance of endogenous transposon transcripts, and flowering time. JMJ14 acts at a point in RNA silencing pathways that is downstream from RNA-dependent RNA polymerase 2 (RDR2) and Argonaute 4 (AGO4). Our results illustrate a link between RNA silencing and demethylation of histone H3 trimethylysine. We propose that JMJ14 acts do...

  16. Transcriptional silencing of the Wnt-antagonist DKK1 by promoter methylation is associated with enhanced Wnt signaling in advanced multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Kinga A Kocemba

    Full Text Available The Wnt/β-catenin pathway plays a crucial role in the pathogenesis of various human cancers. In multiple myeloma (MM, aberrant auto-and/or paracrine activation of canonical Wnt signaling promotes proliferation and dissemination, while overexpression of the Wnt inhibitor Dickkopf1 (DKK1 by MM cells contributes to osteolytic bone disease by inhibiting osteoblast differentiation. Since DKK1 itself is a target of TCF/β-catenin mediated transcription, these findings suggest that DKK1 is part of a negative feedback loop in MM and may act as a tumor suppressor. In line with this hypothesis, we show here that DKK1 expression is low or undetectable in a subset of patients with advanced MM as well as in MM cell lines. This absence of DKK1 is correlated with enhanced Wnt pathway activation, evidenced by nuclear accumulation of β-catenin, which in turn can be antagonized by restoring DKK1 expression. Analysis of the DKK1 promoter revealed CpG island methylation in several MM cell lines as well as in MM cells from patients with advanced MM. Moreover, demethylation of the DKK1 promoter restores DKK1 expression, which results in inhibition of β-catenin/TCF-mediated gene transcription in MM lines. Taken together, our data identify aberrant methylation of the DKK1 promoter as a cause of DKK1 silencing in advanced stage MM, which may play an important role in the progression of MM by unleashing Wnt signaling.

  17. Screening of 397 chemicals and development of a quantitative structure-activity relationship model for androgen receptor antagonism

    DEFF Research Database (Denmark)

    Vinggaard, Annemarie; Niemelä, Jay Russell; Wedebye, Eva Bay; Jensen, Gunde Egeskov

    2008-01-01

    We have screened 397 chemicals for human androgen receptor (AR) antagonism by a sensitive reporter gene assay to generate data for the development of a quantitative structure-activity relationship (QSAR) model. A total of 523 chemicals comprising data on 292 chemicals from our laboratory and data...... synthetic androgen R1881. The MultiCASE expert system was used to construct a QSAR model for AR antagonizing potential. A "5 Times, 2-Fold 50% Cross Validation" of the model showed a sensitivity of 64%, a specificity of 84%, and a concordance of 76%. Data for 102 chemicals were generated for an external...... validation of the model resulting in a sensitivity of 57%, a specificity of 98%, and a concordance of 92% of the model. The model was run on a set of 176103 chemicals, and 47% were within the domain of the model. Approximately 8% of chemicals was predicted active for AR antagonism. We conclude that the...

  18. Dynamical transitions in a pollination-herbivory interaction: a conflict between mutualism and antagonism.

    Directory of Open Access Journals (Sweden)

    Tomás A Revilla

    Full Text Available Plant-pollinator associations are often seen as purely mutualistic, while in reality they can be more complex. Indeed they may also display a diverse array of antagonistic interactions, such as competition and victim-exploiter interactions. In some cases mutualistic and antagonistic interactions are carried-out by the same species but at different life-stages. As a consequence, population structure affects the balance of inter-specific associations, a topic that is receiving increased attention. In this paper, we developed a model that captures the basic features of the interaction between a flowering plant and an insect with a larval stage that feeds on the plant's vegetative tissues (e.g. leaves and an adult pollinator stage. Our model is able to display a rich set of dynamics, the most remarkable of which involves victim-exploiter oscillations that allow plants to attain abundances above their carrying capacities and the periodic alternation between states dominated by mutualism or antagonism. Our study indicates that changes in the insect's life cycle can modify the balance between mutualism and antagonism, causing important qualitative changes in the interaction dynamics. These changes in the life cycle could be caused by a variety of external drivers, such as temperature, plant nutrients, pesticides and changes in the diet of adult pollinators.

  19. A phosphomimetic-based mechanism of dengue virus to antagonize innate immunity.

    Science.gov (United States)

    Chan, Ying Kai; Gack, Michaela U

    2016-05-01

    14-3-3 proteins regulate biological processes by binding to phosphorylated serine or phosphorylated threonine motifs of cellular proteins. Among the 14-3-3 proteins, 14-3-3ɛ serves a crucial function in antiviral immunity by mediating the cytosol-to-mitochondrial membrane translocation of the pathogen sensor RIG-I. Here we found that the NS3 protein of dengue virus (DV) bound to 14-3-3ɛ and prevented translocation of RIG-I to the adaptor MAVS and thereby blocked antiviral signaling. Intriguingly, a highly conserved phosphomimetic RxEP motif in NS3 was essential for the binding of 14-3-3ɛ. A recombinant mutant DV deficient in binding to 14-3-3ɛ showed impairment in antagonism of RIG-I and elicited a markedly augmented innate immune response and enhanced T cell activation. Our work reveals a novel phosphomimetic-based mechanism for viral antagonism of 14-3-3-mediated immunity, which might guide the rational design of therapeutics. PMID:26998762

  20. Antagonism by hemoglobin of effects induced by L-arginine in neuromuscular preparations from rats

    Directory of Open Access Journals (Sweden)

    C.R. Ambiel

    2001-04-01

    Full Text Available Nitric oxide (NO-synthase is present in diaphragm, phrenic nerve and vascular smooth muscle. It has been shown that the NO precursor L-arginine (L-Arg at the presynaptic level increases the amplitude of muscular contraction (AMC and induces tetanic fade when the muscle is indirectly stimulated at low and high frequencies, respectively. However, the precursor in muscle reduces AMC and maximal tetanic fade when the preparations are stimulated directly. In the present study the importance of NO synthesized in different tissues for the L-Arg-induced neuromuscular effects was investigated. Hemoglobin (50 nM did not produce any neuromuscular effect, but antagonized the increase in AMC and tetanic fade induced by L-Arg (9.4 mM in rat phrenic nerve-diaphragm preparations. D-Arg (9.4 mM did not produce any effect when preparations were stimulated indirectly at low or high frequency. Hemoglobin did not inhibit the decrease of AMC or the reduction in maximal tetanic tension induced by L-Arg in preparations previously paralyzed with d-tubocurarine and directly stimulated. Since only the presynaptic effects induced by L-Arg were antagonized by hemoglobin, the present results suggest that NO synthesized in muscle acts on nerve and skeletal muscle. Nevertheless, NO produced in nerve and vascular smooth muscle does not seem to act on skeletal muscle.

  1. Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35

    Energy Technology Data Exchange (ETDEWEB)

    Leung, Daisy W.; Prins, Kathleen C.; Borek, Dominika M.; Farahbakhsh, Mina; Tufariello, JoAnn M.; Ramanan, Parameshwaran; Nix, Jay C.; Helgeson, Luke A.; Otwinowski, Zbyszek; Honzatko, Richard B.; Basler, Christopher F.; Amarasinghe, Gaya K. (Sinai); (Iowa State); (LBNL); (UTSMC)

    2010-03-12

    Ebola viral protein 35 (VP35), encoded by the highly pathogenic Ebola virus, facilitates host immune evasion by antagonizing antiviral signaling pathways, including those initiated by RIG-I-like receptors. Here we report the crystal structure of the Ebola VP35 interferon inhibitory domain (IID) bound to short double-stranded RNA (dsRNA), which together with in vivo results reveals how VP35-dsRNA interactions contribute to immune evasion. Conserved basic residues in VP35 IID recognize the dsRNA backbone, whereas the dsRNA blunt ends are 'end-capped' by a pocket of hydrophobic residues that mimic RIG-I-like receptor recognition of blunt-end dsRNA. Residues critical for RNA binding are also important for interferon inhibition in vivo but not for viral polymerase cofactor function of VP35. These results suggest that simultaneous recognition of dsRNA backbone and blunt ends provides a mechanism by which Ebola VP35 antagonizes host dsRNA sensors and immune responses.

  2. [Calcium antagonism by papaverine in isolated rat gastric fundus strips in a model system].

    Science.gov (United States)

    Simon, L; Sallai, J; Szontagh, M; Simon-Talpas, G; Müller, A

    1984-04-01

    Examining isolated strips of gastric fundus tissue of rats the authors observed that papaverin up to 7.8 X 10(-8) to 6.25 X 10(-7) mol/l increased the intensity of convulsions induced by constant amounts of barium chloride (9.5 X 10(-4); with further increase of the concentration the intensity of convulsions gradually sank under the initial value. An increased proneness to cramping was also observed when the calcium content of the Tyrode solution was reduced. In this case the proneness to cramping was highest between 1 and 1.3 mmol/l calcium content. When the calcium content was 1 mmol/l, papaverin increased the proneness to cramping only to a smaller degree, in agreement with the effect measured when the calcium content of the organ bath was reduced below 1 mmol/l. In model experiments, calcium antagonized the potential difference-increasing effect of papaverin at the ether/NaCl (0.1 mol/l) phase boundary. From this the authors infer an interaction (complex formation) between papaverin and calcium at the phase boundary, which is independent of the biological medium. Their findings and the papaverin -calcium antagonism first observed by Benigni [2] can be interpreted in this way. PMID:6739529

  3. Role of sensitive test-cultures in manifestation of antagonism by human symbiotic bacteria

    Directory of Open Access Journals (Sweden)

    Semenov А.V.

    2011-06-01

    Full Text Available Aim. The study considers the influence of sensitive test-cultures on antagonistic activity and production antimicrobial factors by indigenous and probiotic microorganisms. Material. The original method has been used. It is based on determination of survival of sensitive test-culture under the action of cultural liquids of antagonist processed by metabolites and peptidoglycan of sensitive culture. Resalts. The important role of sensitive test-culture in manifestation of the antagonism active microorganisms has been proved. Received data have proved that antagonistic bacterial activity is a result of cross-species interaction between active and sensitive cultures. The effectors are antimicrobial factors and their regulators. The ability of bacterial peptidoglycan to regulate the cross-species interaction between prokaryotes has been firstly shown. Conclusion. The article concludes that the investigation has revealed new mechanisms of colonization resistance of biotope. It has opened prospects of development of principal new probiotic, prebiotic, sinbiotic, biologically active additive and functional products on the basis of microbial stimulators of bacterial antagonism

  4. Analysis of agonist dissociation constants as assessed by functional antagonism in guinea pig left atria

    International Nuclear Information System (INIS)

    In electrically driven guinea pig left atria, positive inotropic responses to (-)-isoprenaline and the selective beta 1-adrenoceptor agonist RO363 were obtained in the absence and in the presence of the functional antagonists adenosine, carbachol, gallopamil, nifedipine, and Ro 03-7894. Each of the functional antagonists reduced the maximum response to both agonists and produced nonparallel rightward shifts in the cumulative concentration effect curves. For both agonists, dissociation constants (KA) were calculated using the equation described by Furchgott (1966) for irreversible antagonism. For RO363, which is a partial agonist with high agonist activity, the equations outlined for functional interaction by Mackay (1981) were also employed to calculate KA values. The KA values obtained by each method were compared with the dissociation constants (KD) for the two agonists determined from their ability to displace the radioligand (-)-[125I]iodocyanopindolol from beta 1-adrenoceptors in guinea pig left atrial membrane preparations. The estimates of KA varied substantially from KD values. The KD values were taken as more accurate estimates of the true values for the dissociation constants because a high degree of correlation exists between pKD and pD2 values for a number of other beta-adrenoceptor agonists that behave as partial agonists and between pKD and pKB values for a number of beta-adrenoceptor antagonists. Thus, it appears that there are serious limitations in the current theory for using functional antagonism as a means of obtaining agonist dissociation constants

  5. Mechanism of INF-γ antagonizing pulmonary fibroblast proliferation stimulated by 60Co γ-rays

    International Nuclear Information System (INIS)

    Objective: To explore the mechanism of IFN-γ antagonizing human pulmonary fibroblasts (HLF) proliferation stimulated by 60Co γ-rays. Methods: The time- and dose-effect of HLF proliferation promoted by TGF-β1 and rat serum after radiation as well as effect of IFN-γ on proliferation were observed by MTT colorimetric methods. Content of TGF-β1 in rat serum and pulmonary tissues after irradiation as well as the effect of IFN-γ on rat serum after radiation promoting HLF to synthesize TGF-β1 were determined by ELISA. Results: TGF-β1 played a role in promoting HLF proliferation. The sera of irradiated rats could promote HLF proliferation and TGF-β1 synthesis, but the effect was inhibited by IFN-γ significantly (P<0.05). The level of TGF-β1 in rat serum and lung tissues gradually increased from 1 to 4 weeks after irradiation. Conclusions: TGF-β1 is involved in the process of γ-rays stimulating HLF proliferation, while IFN-γ can inhibit HLF from synthesizing TGF-β1 and antagonize its role of promoting HLF proliferation. (authors)

  6. Microwave facilitation of domperidone antagonism of apomorphine-induced stereotypic climbing in mice

    Energy Technology Data Exchange (ETDEWEB)

    Quock, R.M.; Kouchich, F.J.; Ishii, T.K.; Lange, D.G.

    1987-01-01

    The dopaminergic agonist apomorphine produced dose-dependent stereotypic climbing behavior in mice housed in cages with vertical bars. This drug effect was competitively inhibited by systemic pretreatment with the centrally acting dopaminergic antagonist haloperidol but not by microwave irradiation (2.45 GHz, 20 mW/cm2, CW, 10 min) nor by systemic pretreatment with domperidone, a dopaminergic antagonist that only poorly penetrates the blood-brain barrier (BBB). Yet when mice were systemically pretreated with domperidone and then subjected to microwave irradiation (as above), the apomorphine effect was significantly reduced. Microwave irradiation also facilitated antagonism of the apomorphine effect by low and otherwise ineffective systemic pretreatment doses of haloperidol. Apomorphine-induced stereotypic climbing behavior was also reduced by domperidone administered intracerebrally, which bypassed the BBB. Exposure of intracerebral domperidone-pretreated animals to microwave irradiation failed to increase the degree of antagonism. These findings indicate that microwave irradiation can facilitate central effects of domperidone, a drug which acts mainly in the periphery. One possible explanation for these findings is that microwave irradiation alters the permeability of the BBB and increases the entry of domperidone to central sites of action.

  7. IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein

    Directory of Open Access Journals (Sweden)

    Jingyou Yu

    2015-10-01

    Full Text Available The interferon-induced transmembrane (IFITM proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env, thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection.

  8. Astaxanthin from psychrotrophic Sphingomonas faeni exhibits antagonism against food-spoilage bacteria at low temperatures.

    Science.gov (United States)

    Mageswari, Anbazhagan; Subramanian, Parthiban; Srinivasan, Ramachandran; Karthikeyan, Sivashanmugam; Gothandam, Kodiveri Muthukaliannan

    2015-10-01

    Food production and processing industry holds a perpetual relationship with microorganisms and their by-products. In the present study, we aimed to identify beneficial cold-adapted bacteria devoid of any food spoilage properties and study their antagonism against common food-borne pathogens at low temperature conditions. Ten isolates were obtained on selective isolation at 5 °C, which were spread across genera Pseudomonas, Sphingomonas, Psychrobacter, Leuconostoc, Rhodococcus, and Arthrobacter. Methanol extracts of strains were found to contain several bioactive metabolites. Among the studied isolates, methanol extracts of S. faeni ISY and Rhodococcus fascians CS4 were found to show antagonism against growth of Escherichia coli, Proteus mirabilis, Enterobacter aerogenes, Listeria monocytogenes and Vibrio fischeri at refrigeration temperatures. Characterization of the abundant yellow pigment in methanol extracts of S. faeni ISY through UV-Vis spectrophotometry, high performance liquid chromatography (HPLC) and mass spectrometry (LC-MS) revealed the presence of astaxanthin, which, owing to its presence in very large amounts and evidenced to be responsible for antagonistic activity of the solvent extract. PMID:26411893

  9. FCJ-156 Hacking the Social: Internet Memes, Identity Antagonism, and the Logic of Lulz.

    Directory of Open Access Journals (Sweden)

    Ryan M. Milner

    2013-12-01

    Full Text Available 4chan and reddit are participatory media collectives undergirded by a “logic of lulz” that favours distanced irony and critique. It often works at the expense of core identity categories like race and gender. However, the logic need not be entirely counterproductive to public discourse. Provided that diverse identities find voice instead of exclusion, these sites may facilitate vibrant, agonistic discussion instead of disenfranchising antagonism. In order to assess this potential for productive agonism, I undertook a critical discourse analysis of these collectives. Emphasising the image memes they produce, I evaluated discourses on race and gender. Both race and gender representations were dominated by familiar stereotypes and partial representations. However, while dissenting perspectives on race were repressed or excluded, dissenting perspectives on gender were vocalised and contested. The ‘logic of lulz’ facilitated both dominance and counter, each articulated with heavy reliance on irony and critique. This logic ambiguously balanced agonism and antagonism, but contestation provided sharper engagement than repression.

  10. Antagonism of kappa opioid mediated effects in the rat by cyclo(Leu-Gly)

    International Nuclear Information System (INIS)

    The effect of cyclo(Leu-Gly) on U-50,488H- induced pharmacological actions was determined in male Sprague-Dawley rats. Intraperitoneal (i.p.) administration of U-50,488H to rats produced analgesia (tail-flick) and increased urinary output. Cyclo (Leu-Gly) antagonized the analgesic response to U-50,488H. A dose of 10 mg/kg (i.p.) of U-50,488H increased the spontaneous urinary output which was anatagonized by cyclo (Leu-Gly). To determine whether cyclo (Leu-Gly) was acting as a kappa-opioid receptor antagonist, the effect of cyclo (Leu-Gly) on the binding of [3H] ethylketocyclazoncine (EKC) to membranes of rat cerebral cortex and spinal cord was determined. The IC50 values of cyclo(Leu-Gly) in displacing [3H]EKC from its binding sites in cortex and spinal cord were 1.44 and 0.40 mM, respectively. Chronic administration of U-50,488H for 4 days induced tolerance to its analgesic effect. The latter was not affected by cyclo(Leu-Gly) given once a day for 4 days. It is concluded that cyclo(Leu-Gly) antagonizes acute actions of U-50,488H and that such effects of cyclo(Leu-Gly) are not mediated via a direct action on kappa-opioid receptors

  11. Characterization and subcellular localization of an RNA silencing suppressor encoded by Rice stripe tenuivirus

    International Nuclear Information System (INIS)

    Rice stripe virus (RSV) is a single-stranded (ss) RNA virus belonging to the genus Tenuivirus. RSV is present in many East Asian countries and causes severe diseases in rice fields, especially in China. In this study, we analyzed six proteins encoded by the virus for their abilities to suppress RNA silencing in plant using a green fluorescent protein (GFP)-based transient expression assay. Our results indicate that NS3 encoded by RSV RNA3, but not other five RSV encoded proteins, can strongly suppress local GFP silencing in agroinfiltrated Nicotiana benthamiana leaves. NS3 can reverse the GFP silencing, it can also prevent long distance spread of silencing signals which have been reported to be necessary for inducing systemic silencing in host plants. The NS3 protein can significantly reduce the levels of small interfering RNAs (siRNAs) in silencing cells, and was found to bind 21-nucleotide ss-siRNA, siRNA duplex and long ssRNA but not long double-stranded (ds)-RNA. Both N and C terminal of the NS3 protein are critical for silencing suppression, and mutation of the putative nuclear localization signal decreases its local silencing suppression efficiency and blocks its systemic silencing suppression. The NS3-GFP fusion protein and NS3 were shown to accumulate predominantly in nuclei of onion, tobacco and rice cells through transient expression assay or immunocytochemistry and electron microscopy. In addition, transgenic rice and tobacco plants expressing the NS3 did not show any apparent alteration in plant growth and morphology, although NS3 was proven to be a pathogenicity determinant in the PVX heterogenous system. Taken together, our results demonstrate that RSV NS3 is a suppressor of RNA silencing in planta, possibly through sequestering siRNA molecules generated in cells that are undergoing gene silencing.

  12. Epigeneitc silencing of ribosomal RNA genes by Mybbp1a

    Directory of Open Access Journals (Sweden)

    Tan Bertrand

    2012-06-01

    Full Text Available Abstract Background Transcription of the ribosomal RNA gene repeats by Pol I occurs in the nucleolus and is a fundamental step in ribosome biogenesis and protein translation. Due to tight coordination between ribosome biogenesis and cell proliferation, transcription of rRNA and stable maintenance of rDNA clusters are thought to be under intricate control by intercalated mechanisms, particularly at the epigenetic level. Methods and Results Here we identify the nucleolar protein Myb-binding protein 1a (Mybbp1a as a novel negative regulator of rRNA expression. Suppression of rDNA transcription by Mybbp1a was linked to promoter regulation as illustrated by its binding to the chromatin around the hypermethylated, inactive rDNA gene promoters. Our data further showed that downregulation of Mybbp1a abrogated the local DNA methylation levels and histone marks associated with gene silencing, and altered the promoter occupancy of various factors such UBF and HDACs, consequently leading to elevated rRNA expression. Mechanistically, we propose that Mybbp1a maintains rDNA repeats in a silenced state while in association with the negative epigenetic modifiers HDAC1/2. Conclusions Results from our present work reveal a previously unrecognized co-repressor role of Mybbp1a in rRNA expression. They are further consistent with the scenario that Mybbp1a is an integral constituent of the rDNA epigenetic regulation that underlies the balanced state of rDNA clusters.

  13. Noise and correlations in genes silenced by small RNA.

    Science.gov (United States)

    Hwa, Terence; Levine, Erel

    2006-03-01

    Many small regulatory RNAs have been identified in prokaryotes and eukaryotes in recent years. In many cases, RNA regulation is found in critical pathways. These include stress response and quorum sensing pathways in bacteria, and cell differentiation and programmed cell death in eukaryotes. In many cases, regulation by small RNA is used in switching off a response program as long as it is not required, allowing for a fast switching on when necessary. Clearly, accidental execution of such a program may bare grave consequences on the cell, and should be avoided. Here we analyze a stochastic model for gene regulation by the most abundant class of small RNA in bacteria. This class of small RNAs acts by base pairing with target mRNAs, silencing its translation and actively promoting its degradation. Importantly, the small RNA molecule is not recycled. Our model suggests that genes silenced by sRNA exhibits smooth noise, as opposed to the bursty noise characteristic to genes repressed at the level of transcription, with coupling between intrinsic noise and global, extrinsic fluctuations. In addition, we investigate how noise propagates through the indirect coupling between different targets of the same sRNA. These features are discussed in the context of circuits exhibiting multi-stability, where protein bursts have strong implications on spontaneous switching.

  14. Sexuality and 'silence' among Khasi youth of Meghalaya, Northeast India.

    Science.gov (United States)

    War, Ryntihlin Jennifer; Albert, Sandra

    2013-01-01

    The importance of sex education has been well documented in the literature, but there exists a lack of research involving indigenous youth in India. This paper describes perceptions, knowledge and attitudes towards sex education, sexuality, pre-marital sex, rape and homosexuality among indigenous students from the matrilineal Khasi tribe attending a university in Meghalaya in northeast India. Qualitative and quantitative data were collected during and after reproductive health, sexuality and life skills courses. Despite the impression of sexual permissiveness of indigenous peoples that exists in India, students reported a societal silence on issues related to sexuality. Lack of appropriate words in the indigenous language potentially contributes to this silence. Although co-habitation is common and culturally acceptable, students disapproved of pre-marital sex. The influence of Christianisation was also perceived in the frequent reference to sin and guilt associated with masturbation, homosexuality, pre-marital sex and abortion. Students reported that the sex education received in school was 'childish' and inadequate for their adult needs. Many had unrealistic images of what constituted 'normal' sex and also blamed women for rape. The majority of indigenous students expressed the need for non-judgmental fora for discussions on sexual health and for sexuality education. PMID:23758496

  15. Evaluation of BACE1 Silencing in Cellular Models

    Directory of Open Access Journals (Sweden)

    Barbara Nawrot

    2009-01-01

    Full Text Available Beta-secretase (BACE1 is the major enzyme participating in generation of toxic amyloid-beta (Aβ peptides, identified in amyloid plaques of Alzheimer's disease (AD brains. Its downregulation results in decreasing secretion of Aβ. Thus, BACE1 silencing by RNAi represents possible strategy for antiamyloid therapy in the treatment of AD. In this study, a series of newly designed sequences of synthetic and vector-encoded siRNAs (pSilencer, pcPURhU6, and lentivirus were tested against overexpressed and endogenous BACE1 in several cell lines and in adult neural progenitor cells, derived from rat hippocampus. SiRNAs active in human, mouse, and rat cell models were shown to diminish the level of BACE1. In HCN A94 cells, two BACE1-specific siRNAs did not alter the expression of genes of BACE2 and several selected genes involved in neurogenesis (Synapsin I, βIII-Tubulin, Calbidin, NeuroD1, GluR2, CREB, MeCP2, PKR, however, remarkable lowering of SCG10 mRNA, coding protein of stathmin family, important in the development of nervous system, was observed.

  16. Inhibition of protein synthesis does not antagonize induction of UV-induced sister-chromatid exchange in xeroderma pigmentosum cells

    International Nuclear Information System (INIS)

    Cycloheximide strongly antagonizes the induction of sisterchromatid exchanges by ethyl methanesulfonate or mitomycin C in human skin fibroblast and xeroderma pigmentosum cells (group A). Analogous behavior has been observed in several other species including Chinese hamster and plant cells. This report documents an exception to that pattern: cycloheximide fails to antagonize UV-induced sister chromatid exchange in xeroderma pigmentosum cells, whereas it does in normal human skin fibroblast cells. A genetic defect in these cells is postulated to alter the UV-mediated DNA recombination process. (author)

  17. Specific degradation of 3' regions of GUS mRNA in posttranscriptionally silenced tobacco lines may be related to 5'-3' spreading of silencing

    DEFF Research Database (Denmark)

    Braunstein, Thomas Hartig; Moury, Benoit; Johannessen, Marina;

    2002-01-01

    Target regions for posttranscriptional silencing of transgenes often reside in the 3' region of the coding sequence, although there are exceptions. To resolve if the target region is determined by the gene undergoing silencing rather than by the structure of the transgene loci or the plant genetic...... coding region but upstream of the last 200 nt. The quantities of small (21-25 nt) RNAs homologous to 5' or 3' regions of the GUS coding sequence were found to correlate approximately with the target strength of the corresponding regions. These results suggest that transgene locus structure and plant...... can act as efficient inducers as well as targets of posttranscriptional silencing, although the 3' region is the predominant target region in the spontaneously silencing transgenic plant lines examined. Finally, we investigated spreading of the target region in the N. benthamiana plants undergoing...

  18. Disruption of Cell-to-Cell Signaling Does Not Abolish the Antagonism of Phaeobacter gallaeciensis toward the Fish Pathogen Vibrio anguillarum in Algal Systems

    OpenAIRE

    Prol García, M. J.; D'Alvise, P. W.; Gram, L

    2013-01-01

    Quorum sensing (QS) regulates Phaeobacter gallaeciensis antagonism in broth systems; however, we demonstrate here that QS is not important for antagonism in algal cultures. QS mutants reduced Vibrio anguillarum to the same extent as the wild type. Consequently, a combination of probiotic Phaeobacter and QS inhibitors is a feasible strategy for aquaculture disease control.

  19. Self-Silencing, Emotional Awareness, and Eating Behaviors in College Women

    Science.gov (United States)

    Shouse, Sarah H.; Nilsson, Johanna

    2011-01-01

    Self-silencing (or the suppression of expressing one's thoughts, feelings, and needs) can have a negative impact on the mental health of women, from depression to disordered eating behaviors. The authors examined the relationship between self-silencing and disordered eating as well as intuitive eating. The authors also explored whether emotional…

  20. Transcription-dependent silencing of inducible convergent transgenes in transgenic mice

    Directory of Open Access Journals (Sweden)

    Calero-Nieto Fernando J

    2010-01-01

    Full Text Available Abstract Background Silencing of transgenes in mice is a common phenomenon typically associated with short multi-copy transgenes. We have investigated the regulation of the highly inducible human granulocyte-macrophage colony-stimulating-factor gene (Csf2 in transgenic mice. Results In the absence of any previous history of transcriptional activation, this transgene was expressed in T lineage cells at the correct inducible level in all lines of mice tested. In contrast, the transgene was silenced in a specific subset of lines in T cells that had encountered a previous episode of activation. Transgene silencing appeared to be both transcription-dependent and mediated by epigenetic mechanisms. Silencing was accompanied by loss of DNase I hypersensitive sites and inability to recruit RNA polymerase II upon stimulation. This pattern of silencing was reflected by increased methylation and decreased acetylation of histone H3 K9 in the transgene. We found that silenced lines were specifically associated with a single pair of tail-to-tail inverted repeated copies of the transgene embedded within a multi-copy array. Conclusions Our study suggests that epigenetic transgene silencing can result from convergent transcription of inverted repeats which can lead to silencing of an entire multi-copy transgene array. This mechanism may account for a significant proportion of the reported cases of transgene inactivation in mice.

  1. Horreur et silence : le personnage de Pierre Cange dans l’œuvre narrative de Vercors

    Directory of Open Access Journals (Sweden)

    Elisabetta Sibilio

    2015-11-01

    Full Text Available Vercors, who achieved fame thanks to his first novel, Le silence de la mer, published undercover in 1942, makes silence one of the main themes in his work. Silence, which is the paradoxical expression of what Vercors calls “la qualité d’homme”, appears in his work according to two major categories: on the one hand the proud and resilient silence of the protagonist of Silence de la mer or of Arnaud, the main character of the short story Le démenti, who loses his life for having maintained an obstinate silence in the hands of his torturers; on the other hand, the guilty and desperate shameful silence of those who had lost their own humanity when faced with the horror of the camps or had hoped to save their lives by col-laborating with the enemy. This paper will examine three of Vercors’ texts, Les armes de la nuit (1946, La puissance du jour (1951 and Le tigre d’Anvers (1986, which have Pierre Cange as protagonist, a member of the Resistance, deported, who through his own experience is faced with the funda-mental theme of silence.

  2. Gene Silencing Triggers Polycomb Repressive Complex 2 Recruitment to CpG Islands Genome Wide

    DEFF Research Database (Denmark)

    Riising, Eva Madi; Vacher-Comet, Itys; Leblanc, Benjamin Olivier;

    2014-01-01

    Polycomb group (PcG) proteins are required for normal differentiation and development and are frequently deregulated in cancer. PcG proteins are involved in gene silencing; however, their role in initiation and maintenance of transcriptional repression is not well defined. Here, we show that knoc...... by default to nontranscribed CGI genes to maintain their silenced state and to protect cell identity....

  3. Down-Regulation of Gene Expression by RNA-Induced Gene Silencing

    Science.gov (United States)

    Travella, Silvia; Keller, Beat

    Down-regulation of endogenous genes via post-transcriptional gene silencing (PTGS) is a key to the characterization of gene function in plants. Many RNA-based silencing mechanisms such as post-transcriptional gene silencing, co-suppression, quelling, and RNA interference (RNAi) have been discovered among species of different kingdoms (plants, fungi, and animals). One of the most interesting discoveries was RNAi, a sequence-specific gene-silencing mechanism initiated by the introduction of double-stranded RNA (dsRNA), homologous in sequence to the silenced gene, which triggers degradation of mRNA. Infection of plants with modified viruses can also induce RNA silencing and is referred to as virus-induced gene silencing (VIGS). In contrast to insertional mutagenesis, these emerging new reverse genetic approaches represent a powerful tool for exploring gene function and for manipulating gene expression experimentally in cereal species such as barley and wheat. We examined how RNAi and VIGS have been used to assess gene function in barley and wheat, including molecular mechanisms involved in the process and available methodological elements, such as vectors, inoculation procedures, and analysis of silenced phenotypes.

  4. Viral suppressors of RNA silencing in Wheat mosaic virus (WMoV)

    Science.gov (United States)

    RNA silencing is the most effective antiviral adaptive defense mechanism mounted in higher plants to combat viral infection and proliferation. However, viruses have developed a variety of efficient counter-defense mechanisms by suppression of RNA silencing (VSR) in order to successfully impede the h...

  5. The Relationship between Organizational Silence and Burnout among Academicians: A Research on Universities in Turkey

    Science.gov (United States)

    Akin, Ugur; Ulusoy, Tarik

    2016-01-01

    The aim of this research is to analyze the relationship between organizational silence and burnout levels of academicians. The study group consisted of 190 academicians, who work in 17 state universities that are located in 15 different provinces of Turkey. Data were collected through Causes of Faculty Members' Silence Scale and Maslach Burnout…

  6. Disrupting the flow : How brief silences in group conversations affect social needs

    NARCIS (Netherlands)

    Koudenburg, Namkje; Postmes, Tom; Gordijn, Ernestine H.

    2011-01-01

    We all know the awkward feeling when a conversation is disrupted by a brief silence. This paper studies why such moments can be unsettling. We suggest that silences are particularly disturbing if they disrupt the conversational flow. In two experiments we examined the effects of a single brief insta

  7. Performing Silence: Gender, Violence, and Resistance in Women's Narratives from Lahaul, India

    Science.gov (United States)

    Bhattacharya, Himika

    2009-01-01

    This article presents two different ways of understanding silence, through a discussion of women's narratives of violence from Lahaul, India. Here I illustrate how feminist ethnography works its way into re-conceptualizing silence as a tool women use to resist existing patriarchal discourses of honor, tribe and nation. (Contains 1 note.)

  8. Protocol: using virus-induced gene silencing to study the arbuscular mycorrhizal symbiosis in Pisum sativum

    DEFF Research Database (Denmark)

    Grønlund, Mette; Olsen, Anne; Johansen, Elisabeth; Jakobsen, Iver

    2010-01-01

    Virus-induced gene silencing (VIGS) is an alternative reverse genetics tool for silencing of genes in some plants, which are difficult to transform. The pea early-browning virus (PEBV) has been developed as a VIGS vector and used in pea for functional analysis of several genes. However, the avail...

  9. Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome.

    Science.gov (United States)

    Colak, Dilek; Zaninovic, Nikica; Cohen, Michael S; Rosenwaks, Zev; Yang, Wang-Yong; Gerhardt, Jeannine; Disney, Matthew D; Jaffrey, Samie R

    2014-02-28

    Epigenetic gene silencing is seen in several repeat-expansion diseases. In fragile X syndrome, the most common genetic form of mental retardation, a CGG trinucleotide-repeat expansion adjacent to the fragile X mental retardation 1 (FMR1) gene promoter results in its epigenetic silencing. Here, we show that FMR1 silencing is mediated by the FMR1 mRNA. The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5' untranslated region, which hybridizes to the complementary CGG-repeat portion of the FMR1 gene to form an RNA·DNA duplex. Disrupting the interaction of the mRNA with the CGG-repeat portion of the FMR1 gene prevents promoter silencing. Thus, our data link trinucleotide-repeat expansion to a form of RNA-directed gene silencing mediated by direct interactions of the trinucleotide-repeat RNA and DNA. PMID:24578575

  10. RNA-mediated gene silencing in the phytopathogenic fungus Bipolaris oryzae.

    Science.gov (United States)

    Moriwaki, Akihiro; Ueno, Makoto; Arase, Sakae; Kihara, Junichi

    2007-04-01

    The Ascomycetous fungus Bipolaris oryzae is the causal agent of brown leaf spot disease in rice and is a model for studying photomorphogenetic responses by near-UV radiation. Targeted gene disruption (knockout) for functional analysis of photomorphogenesis-related genes in B. oryzae can be achieved by homologous recombination with low efficiency. Here, the applicability of RNA silencing (knockdown) as a tool for targeting endogenous genes in B. oryzae is reported. A polyketide synthase gene (PKS1), involved in fungal DHN melanin biosynthesis pathways, was targeted by gene silencing as a marker. The silencing vector encoding hairpin RNA of the PKS1 fragment was constructed in a two-step PCR-based cloning, and introduced into the B. oryzae genomic DNA. Silencing of the PKS1 gene resulted in albino phenotypes and reduction of PKS1 mRNA expression. These results demonstrate the applicability of targeted gene silencing as a useful reverse-genetics approach in B. oryzae. PMID:17227462

  11. L’architecture du silence de la Shoah dans les fictions de Sylvie Germain

    Directory of Open Access Journals (Sweden)

    José Luis Arráez Llobregat

    2015-11-01

    Full Text Available Silences concerning the Shoah constitute a leitmotiv in Sylvie Germain’s narrative work. Motive and motivation intentionally emerge as a proteiform phenomenon from the writer-philosopher’s genius and from the historical and ideological substance, which imbue the novelist in every sec-tion of her literary creation. The pur-pose of this study is to interpret those silences in a set of selected novels where the Shoah takes up either a primary or a secondary role, but in any case a relevant one. To this end this study carries out a detailed study of the silence coming from the narrator’s origin, the victims, the murderers or God. Beyond the silence in humans and supreme beings, this study also investigates the spatial silence in that apocalyptic world.

  12. Stability of Barley stripe mosaic virus-induced gene silencing in barley

    DEFF Research Database (Denmark)

    Bruun-Rasmussen, Marianne; Madsen, Christian Toft; Jessing, Stine;

    2007-01-01

    for barley and wheat; however, silencing using this vector is generally transient, with efficient silencing often being confined to the first two or three systemically infected leaves. To investigate this further, part of the barley Phytoene desaturase (PDS) gene was inserted into BSMV and the...... length influenced stability but not efficiency of VIGS. Silencing was transient in most cases; however, the decrease in PDS mRNA levels measured by qRT-PCR began earlier and lasted longer than the photobleaching. Occasionally, silencing persisted and could be transmitted through seed as well as via......Virus-induced gene silencing (VIGS) can be used as a powerful tool for functional genomics studies in plants. With this approach, it is possible to target most genes and downregulate the messenger (m)RNA in a sequence-specific manner. Barley stripe mosaic virus (BSMV) is an established VIGS vector...

  13. Simple gene silencing using the trans-acting siRNA pathway.

    Science.gov (United States)

    Jacobs, Thomas B; Lawler, Noah J; LaFayette, Peter R; Vodkin, Lila O; Parrott, Wayne A

    2016-01-01

    In plants, particular micro-RNAs (miRNAs) induce the production of a class of small interfering RNAs (siRNA) called trans-acting siRNA (ta-siRNA) that lead to gene silencing. A single miRNA target is sufficient for the production of ta-siRNAs, which target can be incorporated into a vector to induce the production of siRNAs, and ultimately gene silencing. The term miRNA-induced gene silencing (MIGS) has been used to describe such vector systems in Arabidopsis. Several ta-siRNA loci have been identified in soybean, but, prior to this work, few of the inducing miRNAs have been experimentally validated, much less used to silence genes. Nine ta-siRNA loci and their respective miRNA targets were identified, and the abundance of the inducing miRNAs varies dramatically in different tissues. The miRNA targets were experimentally verified by silencing a transgenic GFP gene and two endogenous genes in hairy roots and transgenic plants. Small RNAs were produced in patterns consistent with the utilization of the ta-siRNA pathway. A side-by-side experiment demonstrated that MIGS is as effective at inducing gene silencing as traditional hairpin vectors in soybean hairy roots. Soybean plants transformed with MIGS vectors produced siRNAs and silencing was observed in the T1 generation. These results complement previous reports in Arabidopsis by demonstrating that MIGS is an efficient way to produce siRNAs and induce gene silencing in other species, as shown with soybean. The miRNA targets identified here are simple to incorporate into silencing vectors and offer an effective and efficient alternative to other gene silencing strategies. PMID:25816689

  14. Suppressors of Defective Silencing in Yeast: Effects on Transcriptional Repression at the Hmr Locus, Cell Growth and Telomere Structure

    OpenAIRE

    Sussel, L; Vannier, D; Shore, D

    1995-01-01

    To identify factors that affect transcriptional silencing at the HMR mating-type locus in yeast, we characterized a set of extragenic suppressor mutations that restore metastable repression in cells containing both a mutant silencer-binding protein (rap1(s)) and a mutated silencer element (hmrδA). A total of 57 suppressors comprising 21 different complementation groups was identified. This report describes a detailed genetic analysis of these suppressors of defective silencing (sds) mutants. ...

  15. A single transgene locus triggers both transcriptional and post-transcriptional silencing through double-stranded RNA production

    OpenAIRE

    Mourrain, Philippe; Blokland, van, R.; Kooter, Jan; Vaucheret, Hervé

    2007-01-01

    Silencing of a target locus by an unlinked silencing locus can result from transcription inhibition (transcriptional gene silencing; TGS) or mRNA degradation (post-transcriptional gene silencing; PTGS), owing to the production of double-stranded RNA (dsRNA) corresponding to promoter or transcribed sequences, respectively. The involvement of distinct cellular components in each process suggests that dsRNA-induced TGS and PTGS likely result from the diversification of an ancient common mechanis...

  16. A campaign against violence: USAID / Kenya funds "Breaking the Silence".

    Science.gov (United States)

    1997-01-01

    From November 25 to December 10, 1996, USAID/Kenya supported 16 days of activism against gender violence. Called "Breaking the Silence," this annual national campaign was aimed at raising awareness of the rising level of violence against women in Kenya. At meeting places around the country, the campaign, organized by the Coalition on Violence Against Women/Kenya and partially funded by USAID/Kenya, brought together hundreds of participants for a dialogue about gender-based violence. Speakers sought to debunk the myths surrounding violence, including the tendency to blame the victims of gender violence. Victims of violence described their treatment at the hands of abusers. Information brochures discussing domestic battery, wife killing, incest, and other forms of violence against women were distributed. USAID/Kenya has provided funding for this coalition since 1995. PMID:12321054

  17. Providing Eligibility Criteria On Turbocharger Filter Silencer Design Processes

    Directory of Open Access Journals (Sweden)

    Adem GÜLERYÜZ

    2013-06-01

    Full Text Available Supply of ventilation air to either the engine room or diesel engine directly affects engine performances. Main criteria is supply of air volume and pressure into the cylinder. When Air starts to come until the cylinders, there many points which behave as restrictions. These are ventilation grills. ventilation fans, ventilation casings, misteliminators, manual or pneumatically adjusted fan dampers, number of bending of ventilation casing, cleanness of casings, air flow speed, air filters, turbocharger filter and silencers, engine’s scavenge air cooler restrictions. Here, we focused on optimum required air need through turbocharger for local diesel engine. While researching actual need, new turbocharger filter were designed and manufactured for engine manufacturer.

  18. Hearing the Silence: Children’s Voices on Violence

    Directory of Open Access Journals (Sweden)

    Kathryn S. Collins

    2003-05-01

    Full Text Available Each year more than five million children in the United States are exposed to traumatizing events in their communities. This paper presents a discussion of multiple areas in violence and victimization research that needs to be continued as well as provides suggestions on how to un-silence child survivors through bridging the gaps between research and practice. It reviews the overarching problem of violence in the U.S. at the domestic and global levels and the effects of victimization. Suggestions on how to study possible mediators and moderators of victimization and individual and family adjustment, including: 1 The ecological perspective; 2 Court process and verdict; and 3Utilization of victim services, are explored. Finally, a rationale and examples of combining qualitative and quantitative methods in future research that uses children’s attributions of violence as a mediator are presented.

  19. Revival of Silenced Echo and Quantum Memory for Light

    CERN Document Server

    Damon, V; Louchet-Chauvet, A; Chanelière, T; Gouët, J -L Le

    2011-01-01

    We propose an original quantum memory protocol. It belongs to the class of rephasing processes and is closely related to two-pulse photon echo. It is known that the strong population inversion produced by the rephasing pulse prevents the plain two-pulse photon echo from serving as a quantum memory scheme. Indeed gain and spontaneous emission generate prohibitive noise. A second $\\pi$-pulse can be used to simultaneously reverse the atomic phase and bring the atoms back into the ground state. Then a secondary echo is radiated from a non-inverted medium, avoiding contamination by gain and spontaneous emission noise. However, one must kill the primary echo, in order to preserve all the information for the secondary signal. In the present work, spatial phase mismatching is used to silence the standard two-pulse echo. An experimental demonstration is presented.

  20. SOCS3 silencing attenuates eosinophil functions in asthma patients.

    Science.gov (United States)

    Zafra, Ma Paz; Cañas, Jose A; Mazzeo, Carla; Gámez, Cristina; Sanz, Veronica; Fernández-Nieto, Mar; Quirce, Santiago; Barranco, Pilar; Ruiz-Hornillos, Javier; Sastre, Joaquín; del Pozo, Victoria

    2015-01-01

    Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process. PMID:25764157

  1. SOCS3 Silencing Attenuates Eosinophil Functions in Asthma Patients

    Directory of Open Access Journals (Sweden)

    Mª Paz Zafra

    2015-03-01

    Full Text Available Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3. In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process.

  2. Linking DNA replication to heterochromatin silencing and epigenetic inheritance

    Institute of Scientific and Technical Information of China (English)

    Qing Li; Zhiguo Zhang

    2012-01-01

    Chromatin is organized into distinct functional domains.During mitotic cell division,both genetic information encoded in DNA sequence and epigenetic information embedded in chromatin structure must be faithfully duplicated.The inheritance of epigenetic states is critical in maintaining the genome integrity and gene expression state.In this review,we will discuss recent progress on how proteins known to be involved in DNA replication and DNA replication-coupled nucleosome assembly impact on the inheritance and maintenance of heterochromatin,a tightly compact chromatin structure that silences gene transcription.As heterochromatin is important in regulating gene expression and maintaining genome stability,understanding how heterochromatin states are inherited during S phase of the cell cycle is of fundamental importance.

  3. Written formative assessment and silence in the classroom

    Science.gov (United States)

    Lee Hang, Desmond Mene; Bell, Beverley

    2015-09-01

    In this commentary, we build on Xinying Yin and Gayle Buck's discussion by exploring the cultural practices which are integral to formative assessment, when it is viewed as a sociocultural practice. First we discuss the role of assessment and in particular oral and written formative assessments in both western and Samoan cultures, building on the account of assessment practices in the Chinese culture given by Yin and Buck. Secondly, we document the cultural practice of silence in Samoan classroom's which has lead to the use of written formative assessment as in the Yin and Buck article. We also discuss the use of written formative assessment as a scaffold for teacher development for formative assessment. Finally, we briefly discuss both studies on formative assessment as a sociocultural practice.

  4. The human HECA interacts with cyclins and CDKs to antagonize Wnt-mediated proliferation and chemoresistance of head and neck cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Dowejko, Albert, E-mail: Albert.Dowejko@klinik.uni-regensburg.de [Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg (Germany); Bauer, Richard; Bauer, Karin [Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg (Germany); Mueller-Richter, Urs D.A. [Department of Oral and Maxillofacial Plastic Surgery, University of Wuerzburg, Pleicherwall 2, 97070 Wuerzburg (Germany); Reichert, Torsten E. [Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg (Germany)

    2012-03-10

    There is a growing evidence that the human homologue of the Drosophila headcase (HECA) plays an important role in human carcinogenesis. So far specific protein interaction partners and affected signaling pathways of HECA are still elusive. In a recent study we showed that HECA overexpression in oral squamous-cell carcinoma (OSCC) keratinocytes has tumor suppressive effects resulting in a recuperation of cell cycle control concerning the entry and progression of S-phase, G2- and M-phase. Currently, quantitative RT-PCR and immunohistochemical analysis of primary tumor tissue from OSCC patients demonstrate that HECA expression is markedly decreased compared to normal control patients with abundant HECA expression. Additionally, there is nearly no HECA expression in OSCC metastases. Here, we show that HECA expression is negatively controlled by the Wnt-pathway and TCF4, a Wnt related transcription factor, binds to the HECA promoter. Furthermore, immunocytochemistry reveals colocalization of HECA with the cyclin dependent kinase CDK9. Immunoprecipitation experiments and proximity ligation assays further reveal an interaction of HECA with CDK2, CDK9, Cyclin A and Cyclin K, a direct transcriptional target of the p53 tumor suppressor. Silencing HECA in OSCC cell lines leads to a significant increase of cell division and a markedly increased resistance against the chemotherapeutic cisplatin. On the contrary, HECA overexpressing OSCC cell lines show decreased resistance of OSCC cells against cisplatin. Therefore, HECA could be considered as future therapeutic agent against Wnt-dependent tumor progression. -- Highlights: Black-Right-Pointing-Pointer HECA is a new cell cycle regulator with anti-tumor features in head and neck cancer. Black-Right-Pointing-Pointer During tumor progression HECA mRNA and protein expression decrease. Black-Right-Pointing-Pointer The HECA promotor is a direct target of the Wnt/beta-catenin/TCF-pathway. Black-Right-Pointing-Pointer The HECA protein

  5. The effects of conformational constraints and steric bulk in the amino acid moiety of philanthotoxins on AMPAR antagonism

    DEFF Research Database (Denmark)

    Jørgensen, Malene; Olsen, Christian A; Mellor, Ian R; Usherwood, Peter N R; Witt, Matthias; Franzyk, Henrik; Jaroszewski, Jerzy W

    2005-01-01

    , establishing general protocols for philanthotoxin solution- and solid-phase synthesis (39-90% and 42-54% overall yields, respectively). The analogues were tested for their ability to antagonize kainate-induced currents of 2-amino-3-(3-hydroxy-5-methyl-4-isoxazoyl)propanoic acid receptors (AMPAR) expressed in...

  6. Self-Regulation in Early Adolescence: Relations with Mother-Son Relationship Quality and Maternal Regulatory Support and Antagonism

    Science.gov (United States)

    Moilanen, Kristin L.; Shaw, Daniel S.; Fitzpatrick, Amber

    2010-01-01

    The purpose of the current investigation was to examine relations among maternal regulatory support, maternal antagonism, and mother-son relationship quality in relation to boys' self-regulation during early adolescence. As part of a larger longitudinal study on 263 low-income, ethnically diverse boys, multiple informants and methods were used to…

  7. SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Relster, Mette Marie; Greve, Katrine Buch Viden;

    2014-01-01

    Polycomb group (PcG) complexes regulate cellular identity through epigenetic programming of chromatin. Here, we show that SSX2, a germline-specific protein ectopically expressed in melanoma and other types of human cancers, is a chromatin-associated protein that antagonizes BMI1 and EZH2 PcG body...

  8. A petunia ethylene-responsive element binding factor, PhERF2, plays an important role in antiviral RNA silencing

    Science.gov (United States)

    Virus-induced gene silencing (VIGS) is a useful technique for functional characterization of plant genes. However, the silencing efficiency of the VIGS system is variable largely depending on compatibility between the host and the virus. Antiviral RNA silencing is involved in plant antiviral defense...

  9. Antagonism between penicillin and erythromycin against Streptococcus pneumoniae in vitro and in vivo

    DEFF Research Database (Denmark)

    Johansen, H K; Jensen, T G; Dessau, R B;

    2000-01-01

    effect of the bactericidal agent. In this study, the possible interaction between penicillin and erythromycin was investigated in vitro and in vivo against four clinical isolates of Streptococcus pneumoniae with MICs of penicillin ranging from 0.016 to 0.5 mg/L and of erythromycin from 0. 25 to >128 mg....../L. In vitro time-kill curves were generated with clinically relevant concentrations of penicillin (10 mg/L) and erythromycin (1 mg/L), either individually or in combination. Antagonism between penicillin and erythromycin was observed for the four isolates. In vivo interaction was investigated in the...... mouse peritonitis model. After intraperitoneal inoculation, penicillin and erythromycin were given either individually or in combination. For two of the four isolates, mortality was significantly higher in the groups treated with the combination of penicillin and erythromycin than in the groups treated...

  10. USP10 Antagonizes c-Myc Transcriptional Activation through SIRT6 Stabilization to Suppress Tumor Formation

    Directory of Open Access Journals (Sweden)

    Zhenghong Lin

    2013-12-01

    Full Text Available The reduced protein expression of SIRT6 tumor suppressor is involved in tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation in human cancers remain unknown. Using a proteomic approach, we have identified the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the SIRT6-interacting proteins. USP10 suppresses SIRT6 ubiquitination to protect SIRT6 from proteasomal degradation. USP10 antagonizes the transcriptional activity of the c-Myc oncogene through SIRT6, as well as p53, to inhibit cell-cycle progression, cancer cell growth, and tumor formation. To support this conclusion, we detected significant reductions in both USP10 and SIRT6 protein expression in human colon cancers. Our study discovered crosstalk between two tumor-suppressive genes in regulating cell-cycle progression and proliferation and showed that dysregulated USP10 function promotes tumorigenesis through SIRT6 degradation.

  11. The absence of antagonism between extracts of Clinacanthus nutans Burm. and Naja naja siamensis venom.

    Science.gov (United States)

    Cherdchu, C; Poopyruchpong, N; Adchariyasucha, R; Ratanabanangkoon, K

    1977-06-01

    Clinacanthus nutans Burm, a herb reputed in Thailand and Malaysia to be "snakebite antidote" has been tested in vitro and in vivo for antivenin activity. The aqueous extract of C. nutans leaves has been found to have no effect on the inhibition of neuromuscular transmission produced by purified Naja naja siamensis neurotoxin in isolated rat phrenic-nerve diaphragm preparations. The extract of C. nutans, when given orally or intraperitoneally, are ineffective in prolonging the survival time of experimental mice receiving lethal doses of N.n. siamensis crude venom. Oral administrations of the herb extracts pretreated with alpha-amylase or beta-amylase also fail to protect the animal. It is concluded that the extract of C. nutans can not antagonize the action of cobra venom. PMID:199949

  12. Combining climate and energy policies: synergies or antagonism? Modeling interactions with energy efficiency instruments

    Energy Technology Data Exchange (ETDEWEB)

    Lecuyer, Oskar [EDF R and D - Efese, 1 av du General de Gaulle, 92141 Clamart (France)] [CIRED, 45 bis av de la Belle-Gabrielle, 94736 Nogent-sur-Marne (France); Bibas, Ruben [CIRED, 45 bis av de la Belle-Gabrielle, 94736 Nogent-sur-Marne (France)

    2012-01-15

    In addition to the already present Climate and Energy package, the European Union (EU) plans to include a binding target to reduce energy consumption. We analyze the rationales the EU invokes to justify such an overlapping and develop a minimal common framework to study interactions arising from the combination of instruments reducing emissions, promoting renewable energy (RE) production and reducing energy demand through energy efficiency (EE) investments. We find that although all instruments tend to reduce GHG emissions and although a price on carbon tends also to give the right incentives for RE and EE, the combination of more than one instrument leads to significant antagonisms regarding major objectives of the policy package. The model allows to show in a single framework and to quantify the antagonistic effects of the joint promotion of RE and EE. We also show and quantify the effects of this joint promotion on ETS permit price, on wholesale market price and on energy production levels. (authors)

  13. [Research on the origins and development of the verse "eighteen antagonism" in Chinese material medica].

    Science.gov (United States)

    Yang, Huan; Fan, Xin-Sheng; Bian, Ya-Li; Li, Yun; Jiang, Chen-Xue

    2013-03-01

    The verse "eighteen antagonism" of Chinese materia medica is a kind of describing of drug nature concerning the incompatibility of drugs in compound prescription. Through organizing the medical books in different historical periods, it is found that the drugs in this verse basically coming from TAO Hong-jing's ben cao jing ji zhu (Variorum of Shennong's Classic of Materia Medica), while the style of verse mostly appeared during the Song-Jin-Yuan period was made. The formed verse was explained and supplemented further in the Ming Dynasty, the basis of which appeared in the Song-Jin-Yuan Dynasty, resulting in the increase of the number of antagonistic drugs and lengthy verse. The origin of the verse seen in Ru men shi qin (Confucians' Duties to Their Parents) and those in other books was not identical and was the most popular one after the Qing Dynasty, becoming the most popularly known even today. PMID:24135473

  14. Dynamics of bounded confidence opinion in heterogeneous social networks: concord against partial antagonism

    CERN Document Server

    Kurmyshev, Evguenii; González-Silva, Ricardo A

    2011-01-01

    Bounded confidence models of opinion dynamics have been actively studied in recent years, in particular, opinion formation and extremism propagation along with other aspects of social dynamics. In this work, after an analysis of limitations of the Deffuant-Weisbuch (DW) bounded confidence, relative agreement model, we propose the Mixed model that takes into account two psychological types of individuals. Concord agents (C-agents) are friendly people; they interact in a way that their opinions get closer always. Agents of the other psychological type show partial antagonism in their interaction (PA-agents). Opinion dynamics in heterogeneous social groups, consisting of agents of the two types, was studied on different social networks. Limit cases of the mixed model, pure C- and PA-societies, were also studied. We found that group opinion formation is, qualitatively, almost independent of the topology of networks used in this work. Opinion fragmentation, polarization and consensus are observed in the mixed mode...

  15. Puerarin antagonizes peroxyntrite-induced injury in retinal pigment epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Lina Hao; Xudong Zhang; Tao Yang; Junling Ma

    2012-01-01

    A rat model of diabetes mellitus was established by intraperitoneal injection of streptozotocin. Three days later, the rats were intraperitoneally administered 140 mg puerarin/kg daily, for a total of 60 successive days. DNA ladder results showed increased apoptosis over time in retinal pigment epithelial cells from rats with streptozotocin-induced diabetes mellitus. Western blot analysis, Reverse transcription-PCR, immunohistochemistry, and flow cytometry results showed increased expression of 3-nitrotyrosine, a peroxyntrite marker, as well as inducible nitric synthase and Fas/FasL, in retinal pigment epithelial cells. Puerarin reversed these changes, and results demonstrated that puerarin inhibited Fas/FasL expression and alleviated peroxyntrite injury to retinal pigment epithelial cells. These results suggested that puerarin inhibited production of inducible nitric oxide synthase and directly antagonized peroxyntrite injury in retinal pigment epithelial cells.

  16. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Maëlle Lempereur

    2016-01-01

    Full Text Available Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L. which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box. In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells. Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif.

  17. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells.

    Science.gov (United States)

    Lempereur, Maëlle; Majewska, Claire; Brunquers, Amandine; Wongpramud, Sumalee; Valet, Bénédicte; Janssens, Philippe; Dillemans, Monique; Van Nedervelde, Laurence; Gallo, Dominique

    2016-01-01

    Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells). Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif. PMID:27190515

  18. Combining climate and energy policies: synergies or antagonism? Modeling interactions with energy efficiency instruments

    International Nuclear Information System (INIS)

    In addition to the already present Climate and Energy package, the European Union (EU) plans to include a binding target to reduce energy consumption. We analyze the rationales the EU invokes to justify such an overlapping and develop a minimal common framework to study interactions arising from the combination of instruments reducing emissions, promoting renewable energy (RE) production and reducing energy demand through energy efficiency (EE) investments. We find that although all instruments tend to reduce GHG emissions and although a price on carbon tends also to give the right incentives for RE and EE, the combination of more than one instrument leads to significant antagonisms regarding major objectives of the policy package. The model allows to show in a single framework and to quantify the antagonistic effects of the joint promotion of RE and EE. We also show and quantify the effects of this joint promotion on ETS permit price, on wholesale market price and on energy production levels. (authors)

  19. Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Lin CHANG; Jian-xin XU; Jing ZHAO; Yong-zheng PANG; Chao-shu TANG; Yong-fen QI

    2004-01-01

    AIM: To observe protective effects of taurine on reactive oxygen species generation induced by homocysteine in rat vascular smooth muscle cells (VSMC). METHODS: Rat VSMC was incubated with various concentrations of homocysteine and taurine. The lactate dehydrogenase (LDH) activity which released into culture medium was elevated as an indicator for VSMC injury. The reactive oxygen species (ROS) - hydrogen peroxide (H2O2) and superoxide anion (O2- )were measured with luminol or lucigenin chemiluminescences method, and the mitochondria Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) were also measured in treated VSMC. RESULTS: LDH leakage from cultured VSMC treated with homocystenie, was increased (P<0.01 vs control), and it was markedly inhibited when co-incubated with taurine (P<0.01). Homocysteine induced H2O2 generation from VSMC in a concentration dependent manner (P<0.01 vs control). However, taurine (5, 10, and 20 mmol/L) significantly antagonized 0.5 mmol/L homocysteine-induced H2O2 generation in VSMC in a concentration dependent manner (P<0.01 vs homocysteine alone group), although taurine itself did not alter the H2O2 generation in VSMC (P>0.05 vs control).In this study, the superoxide anion in VSMC was not detectable by chemiluminent method. In addition, treatment of VSMC with taurine increased mitochondria Mn-SOD and CAT activity in a concentration dependent manner (P<0.05), but homocysteine decreased mitochondria Mn-SOD and CAT activity (P<0.01 vs control). In addition,co-administration of taurine markedly ameliorated homocysteine-induced inhibition of Mn-SOD and CAT activity in VSMC (P<0.01 vs homocysteine alone group). CONCLUSION: Taurine antagonized the effects of homocysteine on ROS generation and anti-oxidant enzyme activities in rat VSMC in vitro.

  20. Frondoside A inhibits breast cancer metastasis and antagonizes prostaglandin E receptors EP4 and EP2.

    Science.gov (United States)

    Ma, Xinrong; Kundu, Namita; Collin, Peter D; Goloubeva, Olga; Fulton, Amy M

    2012-04-01

    Frondoside A, derived from the sea cucumber Cucumaria frondosa has demonstrable anticancer activity in several models, however, the ability of Frondoside A to affect tumor metastasis has not been reported. Using a syngeneic murine model of metastatic breast cancer, we now show that Frondoside A has potent antimetastatic activity. Frondoside A given i.p. to mice bearing mammary gland-implanted mammary tumors, inhibits spontaneous tumor metastasis to the lungs. The elevated Cyclooxygenase-2 activity in many malignancies promotes tumor growth and metastasis by producing high levels of PGE(2) which acts on the prostaglandin E receptors, chiefly EP4 and EP2. We examined the ability of Frondoside A to modulate the functions of these EP receptors. We now show that Frondoside A antagonizes the prostaglandin E receptors EP2 and EP4. (3)H-PGE(2) binding to recombinant EP2 or EP4-expressing cells was inhibited by Frondoside A at low μM concentrations. Likewise, EP4 or EP2-linked activation of intracellular cAMP as well as EP4-mediated ERK1/2 activation were also inhibited by Frondoside A. Consistent with the antimetastatic activity observed in vivo, migration of tumor cells in vitro in response to EP4 or EP2 agonists was also inhibited by Frondoside A. These studies identify a new function for an agent with known antitumor activity, and show that the antimetastatic activity may be due in part to a novel mechanism of action. These studies add to the growing body of evidence that Frondoside A may be a promising new agent with potential to treat cancer and may also represent a potential new modality to antagonize EP4. PMID:21761157

  1. RAB-7 antagonizes LET-23 EGFR signaling during vulva development in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Olga Skorobogata

    Full Text Available The Rab7 GTPase regulates late endosome trafficking of the Epidermal Growth Factor Receptor (EGFR to the lysosome for degradation. However, less is known about how Rab7 activity, functioning late in the endocytic pathway, affects EGFR signaling. Here we used Caenorhabditis elegans vulva cell fate induction, a paradigm for genetic analysis of EGFR/Receptor Tyrosine Kinase (RTK signaling, to assess the genetic requirements for rab-7. Using a rab-7 deletion mutant, we demonstrate that rab-7 antagonizes LET-23 EGFR signaling to a similar extent, but in a distinct manner, as previously described negative regulators such as sli-1 c-Cbl. Epistasis analysis places rab-7 upstream of or in parallel to lin-3 EGF and let-23 EGFR. However, expression of gfp::rab-7 in the Vulva Presursor Cells (VPCs is sufficient to rescue the rab-7(- VPC induction phenotypes indicating that RAB-7 functions in the signal receiving cell. We show that components of the Endosomal Sorting Complex Required for Transport (ESCRT-0, and -I, complexes, hgrs-1 Hrs, and vps-28, also antagonize signaling, suggesting that LET-23 EGFR likely transits through Multivesicular Bodies (MVBs en route to the lysosome. Consistent with RAB-7 regulating LET-23 EGFR trafficking, rab-7 mutants have increased number of LET-23::GFP-positive endosomes. Our data imply that Rab7, by mediating EGFR trafficking and degradation, plays an important role in downregulation of EGFR signaling. Failure to downregulate EGFR signaling contributes to oncogenesis, and thus Rab7 could possess tumor suppressor activity in humans.

  2. The RNA binding domain of Pumilio antagonizes poly-adenosine binding protein and accelerates deadenylation.

    Science.gov (United States)

    Weidmann, Chase A; Raynard, Nathan A; Blewett, Nathan H; Van Etten, Jamie; Goldstrohm, Aaron C

    2014-08-01

    PUF proteins are potent repressors that serve important roles in stem cell maintenance, neurological processes, and embryonic development. These functions are driven by PUF protein recognition of specific binding sites within the 3' untranslated regions of target mRNAs. In this study, we investigated mechanisms of repression by the founding PUF, Drosophila Pumilio, and its human orthologs. Here, we evaluated a previously proposed model wherein the Pumilio RNA binding domain (RBD) binds Argonaute, which in turn blocks the translational activity of the eukaryotic elongation factor 1A. Surprisingly, we found that Argonautes are not necessary for repression elicited by Drosophila and human PUFs in vivo. A second model proposed that the RBD of Pumilio represses by recruiting deadenylases to shorten the mRNA's polyadenosine tail. Indeed, the RBD binds to the Pop2 deadenylase and accelerates deadenylation; however, this activity is not crucial for regulation. Rather, we determined that the poly(A) is necessary for repression by the RBD. Our results reveal that poly(A)-dependent repression by the RBD requires the poly(A) binding protein, pAbp. Furthermore, we show that repression by the human PUM2 RBD requires the pAbp ortholog, PABPC1. Pumilio associates with pAbp but does not disrupt binding of pAbp to the mRNA. Taken together, our data support a model wherein the Pumilio RBD antagonizes the ability of pAbp to promote translation. Thus, the conserved function of the PUF RBD is to bind specific mRNAs, antagonize pAbp function, and promote deadenylation. PMID:24942623

  3. Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation.

    Science.gov (United States)

    Rossbach, Kristine; Wendorff, Stephanie; Sander, Kerstin; Stark, Holger; Gutzmer, Ralf; Werfel, Thomas; Kietzmann, Manfred; Bäumer, Wolfgang

    2009-01-01

    Effects of the histamine H(4) receptor antagonist JNJ 7777120 (1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine) were tested in two models of allergic contact dermatitis. Dermatitis was induced by 2,4-dinitrochlorobenzene and toluene-2,4-diisocyanate, which differ in their Th1-Th2 profile in that way that 2,4-dinitrochlorobenzene is a classical contact allergen with a pronounced Th1-mediated inflammation, while the respiratory chemical allergen toluene-2,4-diisocyanate induces a Th2-dominated inflammation. JNJ 7777120 (15 mg/kg) administered 2 h and 30 min before and 1 h after challenge did not reduce the hapten-induced ear swelling determined 24 h after challenge. This was confirmed by histological evaluation of the ear skin. A repeated administration of the haptens to the rostral part of the back of sensitized animals resulted in a frequent scratching behaviour. An administration of JNJ 7777120 (15 mg/kg) 30 min before challenge reduced this hapten-induced scratching significantly. The H(1) receptor antagonist cetirizine also reduced the scratching bouts in sensitized mice. A combination of H(1) and H(4) receptor antagonists resulted in the strongest inhibition of scratching behaviour associated with allergic dermatitis. These results indicate that H(4) receptor antagonism fails to reduce the allergic inflammatory response but strongly inhibits allergen-induced itch. Thus, a combination of H(4) and H(1) receptor antagonism might be a new strategy to treat pruritus related to allergic diseases like atopic dermatitis. PMID:18647342

  4. Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer.

    Science.gov (United States)

    Singhal, Hari; Greene, Marianne E; Tarulli, Gerard; Zarnke, Allison L; Bourgo, Ryan J; Laine, Muriel; Chang, Ya-Fang; Ma, Shihong; Dembo, Anna G; Raj, Ganesh V; Hickey, Theresa E; Tilley, Wayne D; Greene, Geoffrey L

    2016-06-01

    The functional role of progesterone receptor (PR) and its impact on estrogen signaling in breast cancer remain controversial. In primary ER(+) (estrogen receptor-positive)/PR(+) human tumors, we report that PR reprograms estrogen signaling as a genomic agonist and a phenotypic antagonist. In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. When both hormones are present, progestin modulates estrogen action, such that responsive transcriptomes, cellular processes, and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Despite this overall correlation, the transcriptome patterns modulated by dual treatment are sufficiently different from individual treatments, such that antagonism of oncogenic processes is both predicted and observed. Combination therapies using the selective PR modulator/antagonist (SPRM) CDB4124 in combination with tamoxifen elicited 70% cytotoxic tumor regression of T47D tumor xenografts, whereas individual therapies inhibited tumor growth without net regression. Our findings demonstrate that PR redirects ER chromatin binding to antagonize estrogen signaling and that SPRMs can potentiate responses to antiestrogens, suggesting that cotargeting of ER and PR in ER(+)/PR(+) breast cancers should be explored. PMID:27386569

  5. SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A.

    Directory of Open Access Journals (Sweden)

    Chelsi D Cassilly

    Full Text Available In order to expand the repertoire of antifungal compounds a novel, high-throughput phenotypic drug screen targeting fungal phosphatidylserine (PS synthase (Cho1p was developed based on antagonism of the toxin papuamide A (Pap-A. Pap-A is a cyclic depsipeptide that binds to PS in the membrane of wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with a homozygous deletion of the CHO1 gene (cho1ΔΔ do not produce PS and are able to survive in the presence of Pap-A. Using this phenotype (i.e. resistance to Pap-A as an indicator of Cho1p inhibition, we screened over 5,600 small molecules for Pap-A resistance and identified SB-224289 as a positive hit. SB-224289, previously reported as a selective human 5-HT1B receptor antagonist, also confers resistance to the similar toxin theopapuamide (TPap-A, but not to other cytotoxic depsipeptides tested. Structurally similar molecules and truncated variants of SB-224289 do not confer resistance to Pap-A, suggesting that the toxin-blocking ability of SB-224289 is very specific. Further biochemical characterization revealed that SB-224289 does not inhibit Cho1p, indicating that Pap-A resistance is conferred by another undetermined mechanism. Although the mode of resistance is unclear, interaction between SB-224289 and Pap-A or TPap-A suggests this screening assay could be adapted for discovering other compounds which could antagonize the effects of other environmentally- or medically-relevant depsipeptide toxins.

  6. SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A

    Science.gov (United States)

    Cassilly, Chelsi D.; Maddox, Marcus M.; Cherian, Philip T.; Bowling, John J.; Hamann, Mark T.; Lee, Richard E.; Reynolds, Todd B.

    2016-01-01

    In order to expand the repertoire of antifungal compounds a novel, high-throughput phenotypic drug screen targeting fungal phosphatidylserine (PS) synthase (Cho1p) was developed based on antagonism of the toxin papuamide A (Pap-A). Pap-A is a cyclic depsipeptide that binds to PS in the membrane of wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with a homozygous deletion of the CHO1 gene (cho1ΔΔ) do not produce PS and are able to survive in the presence of Pap-A. Using this phenotype (i.e. resistance to Pap-A) as an indicator of Cho1p inhibition, we screened over 5,600 small molecules for Pap-A resistance and identified SB-224289 as a positive hit. SB-224289, previously reported as a selective human 5-HT1B receptor antagonist, also confers resistance to the similar toxin theopapuamide (TPap-A), but not to other cytotoxic depsipeptides tested. Structurally similar molecules and truncated variants of SB-224289 do not confer resistance to Pap-A, suggesting that the toxin-blocking ability of SB-224289 is very specific. Further biochemical characterization revealed that SB-224289 does not inhibit Cho1p, indicating that Pap-A resistance is conferred by another undetermined mechanism. Although the mode of resistance is unclear, interaction between SB-224289 and Pap-A or TPap-A suggests this screening assay could be adapted for discovering other compounds which could antagonize the effects of other environmentally- or medically-relevant depsipeptide toxins. PMID:27183222

  7. BEX1 Promotes Imatinib-Induced Apoptosis by Binding to and Antagonizing BCL-2

    OpenAIRE

    Qian Xiao; Yeting Hu; Yue Liu; Zhanhuai Wang; Haitao Geng; Lifeng Hu; Dengyong Xu; Ke Wang; Lei Zheng; Shu Zheng; Kefeng Ding

    2014-01-01

    An enhanced anti-apoptotic capacity of tumor cells plays an important role in the process of breakpoint cluster region/Abelson tyrosine kinase gene (BCR/ABL)-independent imatinib resistance. We have previously demonstrated that brain expressed X-linked 1 (BEX1) was silenced in secondary imatinib-resistant K562 cells and that re-expression of BEX1 can restore imatinib sensitivity resulting in the induction of apoptosis. However, the mechanism by which BEX1 executes its pro-apoptotic function r...

  8. Metformin may antagonize Lin28 and/or Lin28B activity, thereby boosting let-7 levels and antagonizing cancer progression.

    Science.gov (United States)

    McCarty, Mark F

    2012-02-01

    Cancer cells with stem cell characteristics are harbored by most tumors, and are characterized by epithelial-mesenchymal transition (EMT) - which promotes invasive growth and metastasis - chemoresistance, and the capacity to reconstitute new tumors. Hence, the control or destruction of cancer stem cells should be a major goal of cancer management. The let-7 family of microRNAs has cancer suppressor activity, and recent evidence suggests that markedly reduced levels of let-7 are not only a typical feature of cancer stem cells, but may be largely responsible for cancer stemness. It is therefore particularly intriguing that metformin, a diabetes drug thought to have potential in the prevention and treatment of cancer, has recently been found to oppose cancer cell stemness, to markedly potentiate chemotherapeutic control of cancer in mouse xenograft models, and to notably boost let-7a levels in cancer stem cells. It is proposed that this latter effect of metformin may reflect AMPK-mediated inhibition of the expression or activity of Lin28/Lin28A, proteins which act post-transcriptionally to decrease the levels of all let-7 family members. The transcription of Lin28B is promoted by NF-kappaB and by Myc; hence, practical measures which antagonize NF-kappaB or Myc activity may complement the utility of metformin for boosting let-7 expression and controlling cancer stemness; salsalate, antioxidants, tyrosine kinase and cox-2 inhibitors, ribavirin, vitamin D, gamma-secretase inhibitors (when available), and parenteral curcumin may have some utility in this regard. Although the impact of histone deacetylase inhibitors on let-7 expression has not been assessed, there is reason to suspect that these drugs might complement let-7's impact on chemoresistance, EMT, and stemness. Multifocal strategies centering on metformin may have considerable potential for reversing cancer stemness and rendering advanced cancers more susceptible to long term control. PMID:22129484

  9. RNA-Interference Components Are Dispensable for Transcriptional Silencing of the Drosophila Bithorax-Complex

    KAUST Repository

    Cernilogar, Filippo M.

    2013-06-13

    Background:Beyond their role in post-transcriptional gene silencing, Dicer and Argonaute, two components of the RNA interference (RNAi) machinery, were shown to be involved in epigenetic regulation of centromeric heterochromatin and transcriptional gene silencing. In particular, RNAi mechanisms appear to play a role in repeat induced silencing and some aspects of Polycomb-mediated gene silencing. However, the functional interplay of RNAi mechanisms and Polycomb group (PcG) pathways at endogenous loci remains to be elucidated.Principal Findings:Here we show that the endogenous Dicer-2/Argonaute-2 RNAi pathway is dispensable for the PcG mediated silencing of the homeotic Bithorax Complex (BX-C). Although Dicer-2 depletion triggers mild transcriptional activation at Polycomb Response Elements (PREs), this does not induce transcriptional changes at PcG-repressed genes. Moreover, Dicer-2 is not needed to maintain global levels of methylation of lysine 27 of histone H3 and does not affect PRE-mediated higher order chromatin structures within the BX-C. Finally bioinformatic analysis, comparing published data sets of PcG targets with Argonaute-2-bound small RNAs reveals no enrichment of these small RNAs at promoter regions associated with PcG proteins.Conclusions:We conclude that the Dicer-2/Argonaute-2 RNAi pathway, despite its role in pairing sensitive gene silencing of transgenes, does not have a role in PcG dependent silencing of major homeotic gene cluster loci in Drosophila. © 2013 Cernilogar et al.

  10. Epigenetic transcriptional silencing and 5-azacytidine-mediated reactivation of a complex transgene in rice.

    Science.gov (United States)

    Kumpatla, S P; Teng, W; Buchholz, W G; Hall, T C

    1997-01-01

    Despite a growing number of reports indicating non-Mendelian inheritance of transgene expression in monocots, no detailed description of the structure and stability of the transgene exists for transformants generated by direct DNA-transfer techniques, making the cause for these observations difficult to determine. In this paper we describe the complex organization of Btt cryIIIA and bar transgenes in rice (Oryza sativa L.) that displayed aberrant segregation in R1 progeny. Silencing rather than rearrangement of the bar gene was implicated because the herbicide-sensitive R1 plants had a DNA hybridization profile identical to that of the resistant R0 parent and R1 siblings. Genomic DNA analysis revealed substantial methylation of the Ubi1/bar sequences in silenced plants and, to a lesser degree, in herbicide-resistant plants, suggesting that the transgene locus was potentiated for silencing. Nuclease protection and nuclear run-on assays confirmed that silencing was due to transcriptional inactivation. Treatment of R2 progeny of silenced plants with 5-azacytidine resulted in demethylation of the Ubi1 promoter and reactivation of bar gene expression, demonstrating a functional relationship for methylation in gene silencing. These findings indicate that methylation-based silencing may be frequent in cereals transformed by direct DNA protocols that insert multiple, often rearranged sequences. PMID:9342860

  11. The dynamics and efficacy of antiviral RNA silencing: A model study

    Directory of Open Access Journals (Sweden)

    Hogeweg Paulien

    2008-03-01

    Full Text Available Abstract Background Mathematical modeling is important to provide insight in the complicated pathway of RNA silencing. RNA silencing is an RNA based mechanism that is widely used by eukaryotes to fight viruses, and to control gene expression. Results We here present the first mathematical model that combines viral growth with RNA silencing. The model involves a plus-strand RNA virus that replicates through a double-strand RNA intermediate. The model of the RNA silencing pathway consists of cleavage of viral RNA into siRNA by Dicer, target cleavage of viral RNA via the RISC complex, and a secondary response. We found that, depending on the strength of the silencing response, different viral growth patterns can occur. Silencing can decrease viral growth, cause oscillations, or clear the virus completely. Our model can explain various observed phenomena, even when they seem contradictory at first: the diverse responses to the removal of RNA dependent RNA polymerase; different viral growth curves; and the great diversity in observed siRNA ratios. Conclusion The model presented here is an important step in the understanding of the natural functioning of RNA silencing in viral infections.

  12. Maternally and Paternally Silenced Imprinted Genes Differ in Their Intron Content

    Directory of Open Access Journals (Sweden)

    Tom Moore

    2006-04-01

    Full Text Available Imprinted genes exhibit silencing of one of the parental alleles during embryonic development. In a previous study imprinted genes were found to have reduced intron content relative to a non-imprinted control set (Hurst et al., 1996. However, due to the small sample size, it was not possible to analyse the source of this effect. Here, we re-investigate this observation using larger datasets of imprinted and control (non-imprinted genes that allow us to consider mouse and human, and maternally and paternally silenced, imprinted genes separately. We find that, in the human and mouse, there is reduced intron content in the maternally silenced imprinted genes relative to a non-imprinted control set. Among imprinted genes, a strong bias is also observed in the distribution of intronless genes, which are found exclusively in the maternally silenced dataset. The paternally silenced dataset in the human is not different to the control set; however, the mouse paternally silenced dataset has more introns than the control group. A direct comparison of mouse maternally and paternally silenced imprinted gene datasets shows that they differ significantly with respect to a variety of intron-related parameters. We discuss a variety of possible explanations for our observations.

  13. Promoter-Bound Trinucleotide Repeat mRNA Drives Epigenetic Silencing in Fragile X Syndrome

    OpenAIRE

    Colak, Dilek; Zaninovic, Nikica; Cohen, Michael S; Rosenwaks, Zev; Yang, Wang-Yong; Gerhardt, Jeannine; Disney, Matthew D.; Jaffrey, Samie R.

    2014-01-01

    Epigenetic gene silencing is seen in several repeat-expansion diseases. In fragile X syndrome, the most common genetic form of mental retardation, a CGG trinucleotide–repeat expansion adjacent to the fragile X mental retardation 1 (FMR1) gene promoter results in its epigenetic silencing. Here, we show that FMR1 silencing is mediated by the FMR1 mRNA. The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5′ untranslated region, which hybridizes to the complementary CGG-repeat ...

  14. MGA2 and SPT23 are modifiers of transcriptional silencing in yeast.

    OpenAIRE

    Dula, M L; Holmes, S G

    2000-01-01

    Transcriptional silencing at the HM loci and telomeres in yeast depends on several trans-acting factors, including Rap1p and the Sir proteins. The SUM1-1 mutation was identified by its ability to restore silencing to strains deficient in one or more of these trans-acting factors. The mechanism by which SUM1-1 bypasses the requirement for silencing proteins is not known. We identified four loci that when reduced in dosage in diploid strains increase the ability of SUM1-1 strains to suppress si...

  15. The C. elegans CSR-1 Argonaute pathway counteracts epigenetic silencing to promote germline gene expression

    OpenAIRE

    Seth, Meetu; Shirayama, Masaki; Gu, Weifeng; Ishidate, Takao; Conte, Darryl; Mello, Craig C

    2013-01-01

    Organisms can develop adaptive sequence-specific immunity by re-expressing pathogen-specific small RNAs that guide gene silencing. For example, the C. elegans PIWI-Argonaute/piRNA pathway recruits RNA-dependent RNA polymerase RdRP to foreign sequences to amplify a trans-generational small RNA-induced epigenetic silencing signal (termed RNAe). Here we provide evidence that in addition to an adaptive memory of silenced sequences, C. elegans can also develop an opposing adaptive memory of expres...

  16. Identification of an RNA Silencing Suppressor from a Plant Double-Stranded RNA Virus

    OpenAIRE

    Cao, Xuesong; Zhou, Peng; Zhang, Xiaoming; Zhu, Shifeng; Zhong, Xuehua; Xiao, Qi; Ding, Biao; Li, Yi

    2005-01-01

    RNA silencing is a mechanism which higher plants and animals have evolved to defend against viral infection in addition to regulation of gene expression for growth and development. As a counterdefense, many plant and some animal viruses studied to date encode RNA silencing suppressors (RSS) that interfere with various steps of the silencing pathway. In this study, we report the first identification of an RSS from a plant double-stranded RNA (dsRNA) virus. Pns10, encoded by S10 of Rice dwarf p...

  17. DICER-LIKE2 Plays a Primary Role in Transitive Silencing of Transgenes in Arabidopsis

    OpenAIRE

    Mlotshwa, Sizolwenkosi; Pruss, Gail J; Peragine, Angela; Endres, Matthew W.; Li, Junjie; Chen, Xuemei; Poethig, R Scott; Bowman, Lewis H.; Vance, Vicki

    2008-01-01

    Dicer-like (DCL) enzymes play a pivotal role in RNA silencing in plants, processing the long double-stranded RNA (dsRNA) that triggers silencing into the primary short interfering RNAs (siRNAs) that mediate it. The siRNA population can be augmented and silencing amplified via transitivity, an RNA-dependent RNA polymerase (RDR)-dependent pathway that uses the target RNA as substrate to generate secondary siRNAs. Here we report that Arabidopsis DCL2–but not DCL4-is required for transitivity in ...

  18. Mod5 protein binds to tRNA gene complexes and affects local transcriptional silencing

    OpenAIRE

    Pratt-Hyatt, Matthew; Pai, Dave A.; Haeusler, Rebecca A.; Wozniak, Glenn G.; Good, Paul D.; Miller, Erin L.; McLeod, Ian X.; Yates, John R.; Hopper, Anita K.; Engelke, David R.

    2013-01-01

    This study provides new insight into the requirements for observed silencing of RNA polymerase II transcription near tRNA genes. Mod5 is a conserved tRNA modification enzyme found in both the nucleus and cytoplasm, although it only modifies tRNAs in the cytoplasm. Mod5 is required for silencing near tRNA genes, and it is bound to both nuclear tRNA gene complexes and nuclear pre-tRNA transcripts. Possible mechanisms for this form of RNA-mediated transcriptional silencing are discussed.

  19. Identification of SAS4 and SAS5, two genes that regulate silencing in Saccharomyces cerevisiae.

    OpenAIRE

    Xu, E Y; S. Kim; Replogle, K; Rine, J; Rivier, D H

    1999-01-01

    In Saccharomyces cerevisiae, chromatin-mediated silencing inactivates transcription of the genes at the HML and HMR cryptic mating-type loci and genes near telomeres. Mutations in the Rap1p and Abf1p binding sites of the HMR-E silencer (HMRa-e**) result in a loss of silencing at HMR. We characterized a collection of 15 mutations that restore the alpha-mating phenotype to MATalpha HMRa-e** strains. These mutations defined three complementation groups, two new groups and one group that correspo...

  20. Honoring silence and valuing community: living leadership in 21st century teaching-learning.

    Science.gov (United States)

    Backer Condon, Barbara; Hegge, Margaret

    2014-04-01

    Leadership is a very personal concept. The methods implemented by leaders often reflect philosophical beliefs and theoretical underpinnings. This column, while recognizing that leadership styles are indeed personal, proffers living leadership in nursing education through two key leadership attitudes. These attitudes are honoring silence and valuing community. Honoring silence is discussed as recognizing the multiple dimensions of silence, and valuing community is presented in light of the humanbecoming community models change concepts: moving-initiating, anchoring-shifting, and pondering-shaping. PMID:24740944

  1. Le silence, ce cri qui résonne dans l’écriture de Viviane Forrester

    Directory of Open Access Journals (Sweden)

    Amelia Peral Crespo

    2015-11-01

    Full Text Available The Holocaust Literature is tied to Silence from its beginning as the writing to silence. Write about the Holocaust and relate the experiences lived in first person or transmit them to the coming generations means leaving the silence which, for years, was the ideal refuge. This research focuses on the literary production of Viviane Forrester. The different expressions of silence that characterize her writings are analyzed. Silence is the cry that underlies in the most profound of the human being that return from the concentration camps, as Lazarus from the dead. It is a silence that grows to a cry because Forrester’s writing, almost in parallel to the fragmentary writing of Blanchot, an-nounces livre à venir, expressing the cry in silence without the ending of the word

  2. Controlling low frequency noise using a passive silencer

    Energy Technology Data Exchange (ETDEWEB)

    DeGagne, D.C.; Faszer, A.C. [Noise Solutions Inc., Calgary, AB (Canada)

    2009-07-01

    Nearly 85 per cent of all the oil and natural gas recovered in Canada comes from Alberta where noise emissions from energy facilities are regulated by the Energy Resources Conservation Board (ERCB) and the Alberta Utilities Commission (AUC) through Noise Control Directive D-038. Operators of energy facilities in Alberta must meet the Permissible Sound Level (PSL) established for industrial facilities that are established for receptor locations such as nearby residences. Despite efforts to manage noise, complaints from nearby residents continue to occur even if the facility is in compliance. This is because high and mid frequency components can decay or be absorbed by air and ground conditions leaving mostly low frequency noise (LFN) at the residence. This paper explored the significance of LFN and how some facility operators are dealing with this problem. The impacts of LFN can range from creating a sensation of pressure in the ear, disturbing normal conversation, to creating secondary vibrating effects within homes. If severe enough, it can also result in potential behavioural dysfunction such as task performance deterioration, sleep disturbance and headaches. In 2006, Noise Solutions Inc. was approached by Hunt Oil Company regarding the installation of a new compressor at their Caroline site. The proposal posed a serious noise problem for the community which requested that the new compressor unit be developed without any additional noise impact on the area. Noise Solutions Inc. used a multi-phased approach to develop the most effective LFN silencer using best practical technology and materials. In an effort to fully attenuate both the high frequency noise (dBA) and the low frequency noise (dBC) of the new compressor unit, Noise Solutions and Hunt Oil agreed that a significant level of sound-suppression would be necessary. The entire noise-suppression unit was specially designed to compensate for the sheer size of the compressor building. The first step to

  3. An Advancement to Reduce Pollution Effectively by Using TI Nanotubes in Aqua Silencer

    Directory of Open Access Journals (Sweden)

    Mankhiar Ajay B

    2014-03-01

    Full Text Available Automobile is the field which is known for pollution in many ways. To overcome pollution many new inventions is existing yet here would be some drawback behind those. This paper is all about Aqua silencer, its working and also the method to overcome the drawback of using charcoal in it. The Aqua Silencer is used in the exhaust to direct the gas from the engine after going through the process of reducing the toxic gases and also water is used to reduce the exhaust noise. In this silencer, the main drawback is using charcoal to reduce the exhaust toxins which should be replaced in the span of 3 years approximately. Hence, in this research I have made an attempt to increase the life time of the silencer functioning by using Titanium Nano-tubes along with charcoal which has the ability to absorb the toxin gases.

  4. A viral suppressor protein inhibits host RNA silencing by hooking up with Argonautes

    KAUST Repository

    Jin, Hailing

    2010-05-01

    RNA viruses are particularly vulnerable to RNAi-based defenses in the host, and thus have evolved specific proteins, known as viral suppressors of RNA silencing (VSRs), as a counterdefense. In this issue of Genes & Development, Azevedo and colleagues (pp. 904-915) discovered that P38, the VSR of Turnip crinkle virus, uses its glycine/tryptophane (GW) motifs as an ARGONAUTE (AGO) hook to attract and disarm the host\\'s essential effector of RNA silencing. Several GW motif-containing cellular proteins are known to be important partners of AGOs in RNA silencing effector complexes in yeast, plants, and animals. The GW motif appears to be a versatile and effective tool for regulating the activities of RNA silencing pathways, and the use of GW mimicry to compete for and inhibit host AGOs may be a strategy used by many pathogens to counteract host RNAi-based defenses. © 2010 by Cold Spring Harbor Laboratory Press.

  5. Identifying Silence Climate in Organizations in the Framework of Contemporary Management Approaches

    Directory of Open Access Journals (Sweden)

    Mustafa Emre Civelek

    2015-10-01

    Full Text Available Dynamic competition conditions in present day, bring about the consequence for businesses to face varied problems with each passing day. At this point, current management approaches include studies that would shed light on the new problems of businesses. Organizational Silence, a concept that has recently been being voiced in business world, has come up in such context. Organizational silence could be expressed as the employee behavior of keeping silent about certain negativities due to various reasons in an organization. Since knowledge sharing in modern organizations is of capital importance in terms of responding hastily to the changes in a competitive environment, spread of this behavior of employees to organization culture and climate presents a threat of indifference. In this study, the concept of Organizational Silence is defined and the effects of conceived silence climate on management of organizations are discussed.

  6. Identifying Silence Climate in Organizations in the Framework of Contemporary Management Approaches

    Directory of Open Access Journals (Sweden)

    Mustafa Emre Civelek

    2015-12-01

    Full Text Available Dynamic competition conditions in present day bring about the consequence for businesses to face varied problems with each passing day. At this point, current management approaches include studies that would shed light on the new problems of businesses. Organizational Silence, a concept that has recently been being voiced in business world, has come up in such context. Organizational silence could be expressed as the employee behavior of keeping silent about certain negativities due to various reasons in an organization. Since knowledge sharing in modern organizations is of capital importance in terms of responding hastily to the changes in a competitive environment, spread of this behavior of employees to organization culture and climate presents a threat of indifference. In this study, the concept of Organizational Silence is defined and the effects of conceived silence climate on management of organizations are discussed.

  7. Reticence in Silence. An Examination of Heidegger's Phenomenology of Language in Contributions to Philosophy

    Czech Academy of Sciences Publication Activity Database

    Nitsche, Martin

    2011-01-01

    Roč. 765, č. 1 (2011), s. 74-79. ISSN 1407-2157 Institutional research plan: CEZ:AV0Z90090514 Keywords : Heidegger * contributions to philosophy * phenomenology * language * reticence in silence Subject RIV: AA - Philosophy ; Religion

  8. Powerful Silences: Becoming a Survivor Through the Construction of Story

    Directory of Open Access Journals (Sweden)

    Arlene Voski Avakian

    2006-09-01

    Full Text Available Survivors’ accounts of traumatic events function on many levels for both the teller and the hearer. By giving voice to what has been silenced, testimonies to the lived experience of trauma challenge dominant perspectives on the meaning and significance of both historical and contemporary events. The construction of these stories and their telling may also provide a means of countering the devastating psychological effects of the trauma. This paper will explore one story about the Turkish genocide of Armenians in 1915 as told to me by my grandmother, Elmas Tutuian. Remarkably consistent over the years of its telling, Tutuian’s story omits as much as it tells. Examining this narrative from both a psychological and a textual perspective, I suggest that by choosing to be silent about parts of her experience, Tutuian constructed herself as a survivor rather than a victim. In choosing to tell her narrative to me, she also shaped my sense of resistance to oppression. The article references works analyzing survivors’ accounts of trauma from a literary, psychological, sociological, theological, and historical perspective.

  9. Modulation of Splicing by Single-Stranded Silencing RNAs.

    Science.gov (United States)

    Liu, Jing; Hu, Jiaxin; Hicks, Jessica A; Prakash, Thazha P; Corey, David R

    2015-06-01

    Single-stranded silencing RNAs (ss-siRNAs) are chemically modified single-stranded oligonucleotides that can function through the cellular RNA interference (RNAi) machinery to modulate gene expression. Because their invention is recent, few studies have appeared describing their use and the potential of ss-siRNAs as a platform for controlling gene expression remains largely unknown. Using oligonucleotides to modulate splicing is an important area for therapeutic development and we tested the hypothesis that ss-siRNAs targeting splice sites might also be capable of directing increased production of therapeutically promising protein isoforms. Here we observe that ss-siRNAs alter splicing of dystrophin. Altered splicing requires a seed sequence complementarity to the target and expression of the RNAi factor argonaute 2. These results demonstrate that ss-siRNAs can be used to modulate splicing, providing another option for therapeutic development programs that aim to increase production of key protein isoforms. Splicing is a classical nuclear process and our data showing that it can be modulated through the action of RNA and RNAi factors offers further evidence that RNAi can take place in mammalian cell nuclei. PMID:25757055

  10. Randomly Amplified Polymorphic DNA of Trichoderma isolates and antagonism against Rhizoctonia solani

    Directory of Open Access Journals (Sweden)

    Larissa Brandão Góes

    2002-06-01

    Full Text Available Random Amplified Polymorphic DNA (RAPD procedure was used to examine the genetic variability among fourteen isolates of Trichoderma and their ability to antagonize Rhizoctonia solani using a dual-culture assay for correlation among RAPD products and their hardness to R. solani. Seven oligodeoxynucleotide primers were selected for the RAPD assays which resulted in 197 bands for 14 isolates of Trichoderma. The data were entered into a binary matrix and a similarity matrix was constructed using DICE similarity (SD index. A UPGMA cluster based on SD values was generated using NTSYS (Numerical Taxonomy System, Applied Biostatistics computer program. A mean coefficient of similarity obtained for pairwise comparisons among the most antagonics isolates was around 40%. The results presented here showed that the variability among the isolates of Trichoderma was very high. No relationship was found between the polymorphism showed by the isolates and their hardness, origin and substrata.A técnica de RAPD (Random Amplified Polymorphic DNA foi utilizada para examinar a variabilidade genética em quatorze isolados de Trichoderma além de sua capacidade de antagonizar o fungo fitopatogênico Rhizoctonia solani usando pareamento in vitro, e a possível relação entre perfís de RAPD e agressividade dos isolados de Trichoderma a R. solani. Foram selecionados sete primers para os ensaios de RAPD, os quais produziram 197 bandas. Os dados foram introduzidos no programa de computador NTSYS (Numerical Taxonomy System, Applied Biostatisticsna forma de uma matrix binária, sendo construída uma matriz de similaridade utilizando-se o coeficiente de similaridade de DICE (SD e baseado nos valores SD, pelo método de agrupamento UPGMA um dendrograma. Observou-se que o grau de similaridade das amostras que apresentaram melhor desempenho antagônico foi bastante baixo, em torno de 40%. Os resultados demonstraram que a variabilidade entre os isolados de Trichoderma é muito

  11. Feasibility Study and Conception of an Intelligent GSM Cell Phone Silencer

    OpenAIRE

    Gorce, Jean-Marie; Kléber, Anja; Valois, Fabrice

    2002-01-01

    The European regulatory authorities are about to change the laws that deal with the proscription of cell phone silencers, towards the acceptance of intelligent systems. This technical report describes a cell phone silencer concept based on the idea of changing the access control parameters on the channel BCCH and develops other intelligent methods, also based on changing parameters on the common downlink channels. Intelligent in the way that they hamper people from using their cellular phones...

  12. Lack of sex chromosome specific meiotic silencing in platypus reveals origin of MSCI in therian mammals

    OpenAIRE

    Daish, Tasman J.; Casey, Aaron E.; Grutzner, Frank

    2015-01-01

    Background In therian mammals heteromorphic sex chromosomes are subject to meiotic sex chromosome inactivation (MSCI) during meiotic prophase I while the autosomes maintain transcriptional activity. The evolution of this sex chromosome silencing is thought to result in retroposition of genes required in spermatogenesis from the sex chromosomes to autosomes. In birds sex chromosome specific silencing appears to be absent and global transcriptional reductions occur through pachytene and sex chr...

  13. Fast silencing reveals a lost role for reciprocal inhibition in locomotion

    OpenAIRE

    Moult, Peter Robert; Cottrell, Glen Alfred; Li, Wenchang

    2013-01-01

    Summary Alternating contractions of antagonistic muscle groups during locomotion are generated by spinal “half-center” networks coupled in antiphase by reciprocal inhibition. It is widely thought that reciprocal inhibition only coordinates the activity of these muscles. We have devised two methods to rapidly and selectively silence neurons on just one side of Xenopus tadpole spinal cord and hindbrain, which generate swimming rhythms. Silencing activity on one side led to rapid cessation of ac...

  14. Enigma of Silence in Organizations: What Happens To Whom and Why?

    OpenAIRE

    Ebru YILDIZ

    2013-01-01

    Özet: Organizational silence, which is defined as being employees remaining silent about their views, opinions and concerns about organizational problems, has recently started to receive due interest in organizational behavior literature. This phenomenon, which poses a great barrier to organizational change and development, is frequently experienced in many organizations. Organizational silence is a composition of various personal and organizational factors and thus has negative impacts an...

  15. Specific Tandem Repeats Are Sufficient for Paramutation-Induced Trans-Generational Silencing

    OpenAIRE

    Belele, Christiane L.; Lyudmila Sidorenko; Maike Stam; Rechien Bader; Arteaga-Vazquez, Mario A.; Chandler, Vicki L.

    2013-01-01

    Paramutation is a well-studied epigenetic phenomenon in which trans communication between two different alleles leads to meiotically heritable transcriptional silencing of one of the alleles. Paramutation at the b1 locus involves RNA-mediated transcriptional silencing and requires specific tandem repeats that generate siRNAs. This study addressed three important questions: 1) are the tandem repeats sufficient for paramutation, 2) do they need to be in an allelic position to mediate paramutati...

  16. Nuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA

    OpenAIRE

    Orzalli, Megan H.; Conwell, Sara E.; Berrios, Christian; DeCaprio, James A.; Knipe, David M.

    2013-01-01

    Cells have evolved mechanisms to silence foreign DNA to prevent the expression of foreign genes within them. In mammalian cells, this involves the assembly of heterochromatin on foreign DNAs such as viral or transfected DNA. Herpesviruses have evolved strategies to counteract these host mechanisms to express their own genes. Herein we demonstrate that the nuclear DNA sensor IFN-inducible protein 16 (IFI16) is involved in the host silencing response to foreign DNA. IFI16 promotes the assembly ...

  17. Reconceptualising the right of silence as an effective fair trial standard

    OpenAIRE

    JACKSON, JOHN

    2009-01-01

    As the European Court of Human Rights has come to qualify the privilege against self-incrimination and the right of silence in recent decisions, this article argues that the Court has failed to provide a convincing rationale for these rights. It is claimed that within the criminal process the right of silence should be distinguished from the privilege against self-incrimination and given enhanced effect in order to uphold the protective and participatory rights of the defence which come into ...

  18. The Effect of Organizational Stress on Organizational Silence: An Application in Five Star Thermal Hotel Establishments

    OpenAIRE

    KILIÇ, Gonca; TUNÇ, Tülin; SARAÇLI, Sinan; KILIÇ, İbrahim

    2013-01-01

    In this study it was aimed to determine the effects of organizational stress on organizational silence with an application at five-stars hotel establishments and to review general literature on organizational stress and organizational silence. Study questionnaires were distributed 387 participants working at five-stars hotel establishments in Afyonkarahisar. Data was analyzed by factor analysis, reliability analysis, mean, standard deviation, Pearson’s correlation analysis, and bivariate ...

  19. AGO/RISC-mediated antiviral RNA silencing in a plant in vitro system

    OpenAIRE

    Schuck, Jana; Gursinsky, Torsten; Pantaleo, Vitantonio; Burgyán, Jozsef; Behrens, Sven-Erik

    2013-01-01

    AGO/RISC-mediated antiviral RNA silencing, an important component of the plant’s immune response against RNA virus infections, was recapitulated in vitro. Cytoplasmic extracts of tobacco protoplasts were applied that supported Tombusvirus RNA replication, as well as the formation of RNA-induced silencing complexes (RISC) that could be functionally reconstituted with various plant ARGONAUTE (AGO) proteins. For example, when RISC containing AGO1, 2, 3 or 5 were programmed with exogenous siRNAs ...

  20. A viral suppressor protein inhibits host RNA silencing by hooking up with Argonautes

    OpenAIRE

    Jin, Hailing; Zhu, Jian-Kang

    2010-01-01

    RNA viruses are particularly vulnerable to RNAi-based defenses in the host, and thus have evolved specific proteins, known as viral suppressors of RNA silencing (VSRs), as a counterdefense. In this issue of Genes & Development, Azevedo and colleagues (pp. 904–915) discovered that P38, the VSR of Turnip crinkle virus, uses its glycine/tryptophane (GW) motifs as an ARGONAUTE (AGO) hook to attract and disarm the host's essential effector of RNA silencing. Several GW motif-containing cellular pro...

  1. Tailor: a computational framework for detecting non-templated tailing of small silencing RNAs

    OpenAIRE

    Chou, Min-Te; Han, Bo W; Hsiao, Chiung-Po; Phillip D Zamore; Weng, Zhiping; Hung, Jui-Hung

    2015-01-01

    Small silencing RNAs, including microRNAs, endogenous small interfering RNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs), have been shown to play important roles in fine-tuning gene expression, defending virus and controlling transposons. Loss of small silencing RNAs or components in their pathways often leads to severe developmental defects, including lethality and sterility. Recently, non-templated addition of nucleotides to the 3′ end, namely tailing, was found to associate with the p...

  2. Silencing of the rotavirus NSP4 protein decreases the incidence of biliary atresia in murine model.

    Directory of Open Access Journals (Sweden)

    Jiexiong Feng

    Full Text Available Biliary atresia is a common disease in neonates which causes obstructive jaundice and progressive hepatic fibrosis. Our previous studies indicate that rotavirus infection is an initiator in the pathogenesis of experimental biliary atresia (BA through the induction of increased nuclear factor-kappaB and abnormal activation of the osteopontin inflammation pathway. In the setting of rotavirus infection, rotavirus nonstructural protein 4 (NSP4 serves as an important immunogen, viral protein 7 (VP7 is necessary in rotavirus maturity and viral protein 4 (VP4 is a virulence determiner. The purpose of the current study is to clarify the roles of NSP4, VP7 and VP4 in the pathogenesis of experimental BA. Primary cultured extrahepatic biliary epithelia were infected with Rotavirus (mmu18006. Small interfering RNA targeting NSP4, VP7 or VP4 was transfected before rotavirus infection both in vitro and in vivo. We analyzed the incidence of BA, morphological change, morphogenesis of viral particles and viral mRNA and protein expression. The in vitro experiments showed NSP4 silencing decreased the levels of VP7 and VP4, reduced viral particles and decreased cytopathic effect. NSP4-positive cells had strongly positive expression of integrin subunit α2. Silencing of VP7 or VP4 partially decreased epithelial injury. Animal experiments indicated after NSP4 silencing, mouse pups had lower incidence of BA than after VP7 or VP4 silencing. However, 33.3% of VP4-silenced pups (N = 6 suffered BA and 50% of pups (N = 6 suffered biliary injury after VP7 silencing. Hepatic injury was decreased after NSP4 or VP4 silencing. Neither VP4 nor VP7 were detected in the biliary ducts after NSP4. All together, NSP4 silencing down-regulates VP7 and VP4, resulting in decreased incidence of BA.

  3. Genetically encoded molecular tools for light-driven silencing of targeted neurons

    OpenAIRE

    Chow, Brian Y.; Han, Xue; Boyden, Edward S.

    2012-01-01

    The ability to silence, in a temporally precise fashion, the electrical activity of specific neurons embedded within intact brain tissue, is important for understanding the role that those neurons play in behaviors, brain disorders, and neural computations. “Optogenetic” silencers, genetically encoded molecules that, when expressed in targeted cells within neural networks, enable their electrical activity to be quieted in response to pulses of light, are enabling these kinds of causal circuit...

  4. Gene Silencing and Polycomb Group Proteins: An Overview of their Structure, Mechanisms and Phylogenetics

    OpenAIRE

    Golbabapour, Shahram; Majid, Nazia Abdul; Hassandarvish, Pouya; Hajrezaie, Maryam; Abdulla, Mahmood Ameen; Hadi, A. Hamid A.

    2013-01-01

    DNA methylation, histone modifications, and chromatin configuration are crucially important in the regulation of gene expression. Among these epigenetic mechanisms, silencing the expression of certain genes depending on developmental stage and tissue specificity is a key repressive system in genome programming. Polycomb (Pc) proteins play roles in gene silencing through different mechanisms. These proteins act in complexes and govern the histone methylation profiles of a large number of genes...

  5. Evaluation of shRNA-mediated gene silencing by electroporation in LPB fibrosarcoma cells:

    OpenAIRE

    Čemažar, Maja; Kamenšek, Urška; Vidic, Suzana

    2008-01-01

    Background. Silencing oncogenes or other genes that contribute to tumor malignancy and progression offers a promising approach to treating cancer. Specific and efficient silencing of gene expression can be achieved by RNA interference (RNAi) technology using small interfering RNA (siRNA) or short hairpin RNA (shRNA). However, a major challenge in RNAi technology is effective delivery of interfering molecules into target cells. The aim of our study was to evaluate electroporation as a perspect...

  6. Post-transcriptional gene silencing signal could move rapidly and bidirectionally in grafted Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    LI Ming; JIANG Shiling; WANG Youqun; LIU Guoqin

    2006-01-01

    RNA interference (RNAi), one of the newly found ways for post-transcriptional gene silencing, has been widely used to investigate gene functions through transgenic methods for introducing an RNA silencing signal into plants. In the present study, we constructed a dexamethazone (DEX)-inducible RNAi binary vector harboring a specific sequence fragment (168-bp) homologous to KatB and KatC, two kinesin isoform genes of Arabidopsis, which were proved to result in the post-transcriptional gene silencing of KatB and KatC in DEX-induced transgenic plants. RT-PCR and Northern blot analysis on transgenic homozygous Arabidopsis (termed as RNAi-type plants) showed that DEX inducement causes KatB and KatC mRNA degradation. With a simplified method, Arabidopsis grafting was effectively performed between RNAi-type and wild-type lines. The target gene mRNA levels were tested based on semi-quantitative RT-PCR. Our results demonstrateed that DEX-induced gene silencing signals could result in a reduction in KatB and KatC mRNA in the wild-type rootstocks or scions, indicating that silencing signals of RNAi could be transmitted bidirectionally across the graft junction whether RNAi-plants were scions or stocks. In contrast to the previously reported results on grafted tobacco, the transmission of post- transcriptional gene silencing signals caused by RNAi in grafted Arabidopsis is more effective than that in tobacco.

  7. The molecular basis for stability of heterochromatin-mediated silencing in mammals

    Directory of Open Access Journals (Sweden)

    Hiragami-Hamada Kyoko

    2009-11-01

    Full Text Available Abstract The archetypal epigenetic phenomenon of position effect variegation (PEV in Drosophila occurs when a gene is brought abnormally close to heterochromatin, resulting in stochastic silencing of the affected gene in a proportion of cells that would normally express it. PEV has been instrumental in unraveling epigenetic mechanisms. Using an in vivo mammalian model for PEV we have extensively investigated the molecular basis for heterochromatin-mediated gene silencing. Here we distinguish 'epigenetic effects' from other cellular differences by studying ex vivo cells that are identical, apart from the expression of the variegating gene which is silenced in a proportion of the cells. By separating cells according to transgene expression we show here that silencing appears to be associated with histone H3 lysine 9 trimethylation (H3K9me3, DNA methylation and the localization of the silenced gene to a specific nuclear compartment enriched in these modifications. In contrast, histone H3 acetylation (H3Ac and lysine 4 di or tri methylation (H3K4me2/3 are the predominant modifications associated with expression where we see the gene in a euchromatic compartment. Interestingly, DNA methylation and inaccessibility, rather than H3K9me3, correlated most strongly with resistance to de-repression by cellular activation. These results have important implications for understanding the contribution of specific factors involved in the establishment and maintenance of gene silencing and activation in vivo.

  8. Sea urchin arylsulfatase insulator exerts its anti-silencing effect without interacting with the nuclear matrix.

    Science.gov (United States)

    Hino, Shinjiro; Akasaka, Koji; Matsuoka, Masao

    2006-03-17

    Chromatin insulators have been shown to stabilize transgene expression. Although insulators have been suggested to regulate the subcellular localization of chromosomes, it is still unclear whether this property is important for their anti-silencing activity. To investigate the underlying mechanisms governing the anti-silencing function of insulators, we studied the association of sea urchin arylsulfatase insulator (ArsI) with the nuclear matrix, which is a key component of the subnuclear localization of the genome. ArsI did not potentiate the nuclear matrix association with the transgene, even though it showed strong anti-silencing activity. This observation was in clear contrast to the results of the experiment using a human interferon-beta scaffold attachment region, in which the anti-silencing effect coincided with the enhanced matrix association. Chromatin immunoprecipitation analyses suggested that the absence of the matrix binding by ArsI was due to a lack of its binding to CCCTC-binding factor (CTCF), a protein known to be associated with matrix binding by chicken beta-globin insulator. Furthermore, ArsI maintained the nucleosome occupancy within the transgene at a constant level during long-term culture, although ArsI itself was not a nucleosome-excluding sequence. Taken together, these results suggest that this insulator exerts its anti-silencing activity by counteracting silencing-associated factors to maintain local chromatin environment, rather than by remodeling the subnuclear localization of the transgene locus. PMID:16426632

  9. Strategy of gene silencing in cassava for validation of resistance genes

    International Nuclear Information System (INIS)

    Cassava (Manihot esculenta) is a major source of food for more than 1000 million people in the world and constitutes an important staple crop. Cassava bacterial blight, caused by the gram negative bacterium Xanthomonas axonopodis pv. manihotis, is one of the most important constraints for this crop. A candidate resistance gene against cassava bacterial blight, named RXam1, has been identified previously. In this work, we employed the gene silencing approach using the African cassava mosaic virus (ACMV) to validate the function of the RXam1 gene. We used as positive control the su gen, which produce photo blanching in leaves when is silenced. Plants from the SG10735 variety were bombardment with the ACMV-A-SU+ACMV-B y ACMV-A-RXam1+ACMV-B constructions. The silencing efficiency employing the su gene was low, only one of seven plants showed photo blanching. In the putative silenced plants for the RXam1 gene, no presence of siRNAs corresponding to RXam1 was observed; although a low diminution of the RXam1 gene expression was obtained. The growth curves for the Xam strain CIO136 in cassava plants inoculated showing a little but no significance difference in the susceptibility in the silenced plants compared to not silenced

  10. Archaerhodopsin Selectively and Reversibly Silences Synaptic Transmission through Altered pH.

    Science.gov (United States)

    El-Gaby, Mohamady; Zhang, Yu; Wolf, Konstantin; Schwiening, Christof J; Paulsen, Ole; Shipton, Olivia A

    2016-08-23

    Tools that allow acute and selective silencing of synaptic transmission in vivo would be invaluable for understanding the synaptic basis of specific behaviors. Here, we show that presynaptic expression of the proton pump archaerhodopsin enables robust, selective, and reversible optogenetic synaptic silencing with rapid onset and offset. Two-photon fluorescence imaging revealed that this effect is accompanied by a transient increase in pH restricted to archaerhodopsin-expressing boutons. Crucially, clamping intracellular pH abolished synaptic silencing without affecting the archaerhodopsin-mediated hyperpolarizing current, indicating that changes in pH mediate the synaptic silencing effect. To verify the utility of this technique, we used trial-limited, archaerhodopsin-mediated silencing to uncover a requirement for CA3-CA1 synapses whose afferents originate from the left CA3, but not those from the right CA3, for performance on a long-term memory task. These results highlight optogenetic, pH-mediated silencing of synaptic transmission as a spatiotemporally selective approach to dissecting synaptic function in behaving animals. PMID:27524609

  11. Neuropeptide Y Y5 receptor antagonism causes faster extinction and attenuates reinstatement in cocaine-induced place preference

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Wörtwein, Gitta; Fink-Jensen, Anders;

    2013-01-01

    present study, we further explored potential anti-addiction-related effects of Y5 antagonism in another murine model of cocaine addiction-related behavior: conditioned place-preference (CPP). Using this model, it was tested whether blockade or deficiency of the NPY Y5 receptor could influence the...... induction, extinction or reinstatement of a conditioned cocaine response. We found that the Y5 antagonist L-152,804 causes faster extinction and reduced reinstatement of cocaine-induced CPP but did not reduce the ability of cocaine to induce CPP. Similarly, Y5-KO mice displayed faster extinction, and...... reinstatement of cocaine-induced CPP was absent. The development of CPP for cocaine was similar between Y5-KO and WT mice. Taken together, the present data show that Y5 antagonism attenuates relapse to cocaine addiction-related behavior. Prevention of relapse is considered to be of pivotal importance for the...

  12. P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yan Deng

    2015-01-01

    Conclusions: The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.

  13. The p122 Subunit of Tobacco Mosaic Virus Replicase Is a Potent Silencing Suppressor and Compromises both Small Interfering RNA- and MicroRNA-Mediated Pathways▿

    OpenAIRE

    Csorba, Tibor; Bovi, Aurelie; Dalmay, Tamás; Burgyán, József

    2007-01-01

    One of the functions of RNA silencing in plants is to defend against molecular parasites, such as viruses, retrotransposons, and transgenes. Plant viruses are inducers, as well as targets, of RNA silencing-based antiviral defense. Replication intermediates or folded viral RNAs activate RNA silencing, generating small interfering RNAs (siRNAs), which are the key players in the antiviral response. Viruses are able to counteract RNA silencing by expressing silencing-suppressor proteins. It has b...

  14. Antagonism in the extraction of uranium(VI) by the binary mixture of PC88A and benzimidazole

    International Nuclear Information System (INIS)

    Extraction studies of uranium(VI) by the binary mixture of PC88A and benzimidazole show an antagonistic behavior in the concentration range 10-5-10-6M of PC88A and 0.005M of benzimidazole. Antagonism is observed due to the deprotonation of PC88A by benzimidazole forming an adduct resulting in the virtual removal of PC88A from the system. (author)

  15. Leptin Analog Antagonizes Leptin Effects on Food Intake and Body Weight but Mimics Leptin-Induced Vagal Afferent Activation

    OpenAIRE

    Peters, J H; Simasko, S. M.; Ritter, R. C.

    2007-01-01

    A recombinantly produced murine leptin analog (MLA) antagonizes leptin-induced signaling in cell lines that express the long form of the leptin receptor. However, the effects of MLA on the activity of leptin-sensitive neurons and on central neural controls of food intake have not been reported. Here we report effects of MLA on food intake and body weight in adult rats and on the activity of cultured rat vagal afferent neurons. Daily intracerebroventricular coinjection of MLA with exogenous le...

  16. Antagonism between two intestinal parasites in humans: the importance of co-infection for infection risk and recovery dynamics

    OpenAIRE

    Blackwell, AD; Martin, M.; Kaplan, H.; Gurven, M

    2013-01-01

    Co-infection may affect transmission and recovery from infection, but remains an understudied element of disease ecology, particularly with regard to antagonism between parasites sharing a host. Helminth and giardia infections are often endemic in the same populations and both occupy the small intestine; yet few studies have examined interactions between these parasites. We report on helminth-giardia co-infections in a panel study of forager-horticulturalists in the Bolivian lowlands. Parasit...

  17. LPS antagonism reduces graft-versus-host disease and preserves graft-versus-leukemia activity after experimental bone marrow transplantation

    OpenAIRE

    Cooke, Kenneth R.; Gerbitz, Armin; Crawford, James M.; Teshima, Takanori; Hill, Geoffrey R.; Tesolin, Amy; Rossignol, Daniel P.; Ferrara, James L.M.

    2001-01-01

    Acute graft-versus-host disease (GVHD) and leukemic relapse remain the two major obstacles to successful outcomes after allogeneic bone marrow transplantation (BMT). Recent studies have demonstrated that the loss of gastrointestinal tract integrity, and specifically the translocation of LPS into the systemic circulation, is critical to the induction of cytokine dysregulation that contributes to GVHD. Using a mouse BMT model, we studied the effects of direct LPS antagonism on GVHD severity and...

  18. Failure of time-kill synergy studies using subinhibitory antimicrobial concentrations to predict in vivo antagonism of cephalosporin-rifampin combinations against Staphylococcus aureus.

    OpenAIRE

    Brandt, C M; Rouse, M S; Tallan, B M; Wilson, W. R.; Steckelberg, J M

    1994-01-01

    Results of in vitro time-kill synergy studies using subinhibitory, inhibitory, or suprainhibitory concentrations of bactericidal agents were compared with treatment outcomes of experimental infective endocarditis due to a methicillin-susceptible strain of Staphylococcus aureus. For rifampin-cephalosporin combinations, in vitro synergy testing using recommended fractions of the MIC failed to predict antagonism in vivo while concentrations above the MIC corresponded with antagonism in vivo.

  19. Antagonism exerted by an association of a Bacteroides thetaiotaomicron strain and a Fusobacterium necrogenes strain against Clostridium perfringens in gnotobiotic mice and in fecal suspensions incubated in vitro.

    OpenAIRE

    Yurdusev, N; Ladire, M; Ducluzeau, R.; Raibaud, P

    1989-01-01

    Antagonism between an association of Bacteroides thetaiotaomicron and Fusobacterium necrogenes strains and two strains of Clostridium perfringens was evidenced both in vivo in gnotobiotic mice and ex vivo in fecal suspensions incubated for 22 h at 37 degrees C. Several features of this antagonism were similar in and ex vivo. (i) An obligate and continuous synergy between B. thetaiotaomicron and F. necrogenes was required; (ii) the two C. perfringens strains did not respond to the same extent ...

  20. Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism

    OpenAIRE

    Allen, Kyle D; Shamji, Mohammed F; Mata, Brian A.; Gabr, Mostafa A; Sinclair, S. Michael; Schmitt, Daniel O.; Richardson, William J.; Setton, Lori A.

    2011-01-01

    Introduction Tumor necrosis factor-α (TNFα) has received significant attention as a mediator of lumbar radiculopathy, with interest in TNF antagonism to treat radiculopathy. Prior studies have demonstrated that TNF antagonists can attenuate heightened nociception resulting from lumbar radiculopathy in the preclinical model. Less is known about the potential impact of TNF antagonism on gait compensations, despite being of clinical relevance. In this study, we expand on previous descriptions of...

  1. Antagonism of CD317 Restriction of Human Immunodeficiency Virus Type 1 (HIV-1) Particle Release and Depletion of CD317 Are Separable Activities of HIV-1 Vpu▿

    OpenAIRE

    Goffinet, Christine; Homann, Stefanie; Ambiel, Ina; Tibroni, Nadine; Rupp, Daniel; Keppler, Oliver T.; Fackler, Oliver T.

    2010-01-01

    Vpu antagonizes human immunodeficiency virus type 1 (HIV-1) particle release inhibition by CD317/BST-2/Tetherin. Whether this Vpu activity strictly requires cellular depletion of the restriction factor is unclear. Here, we characterized CD317 variants with mutations in putative sorting or ubiquitination motifs. All mutants still potently impaired release of Vpu-defective HIV-1 and remained sensitive to Vpu-mediated release enhancement. Importantly, this virological antagonism correlated with ...

  2. Contributions of phenolics and added vitamin C to the antioxidant capacity of pomegranate and grape juices: synergism and antagonism among constituents†

    OpenAIRE

    Bolling, Bradley W.; Chen, Ya-Yen; Chen, C-Y Oliver

    2013-01-01

    The aim of this study was to examine the contribution of sugar, organic acid, neutral phenol, and anthocyanin fractions and added ascorbic acid to grape and pomegranate-nectarine juice total phenol, ORAC, FRAP, and DPPH values. Neutral phenol and anthocyanin fractions contributed ≥75% of the total antioxidant capacity (TAC) for both juices. Intrinsic synergy and antagonism among the fractionated constituents occurred inconsistently in each assay. Sugars and organic acids antagonized pomegrana...

  3. TRPV1 Antagonism by Capsazepine Modulates Innate Immune Response in Mice Infected with Plasmodium berghei ANKA

    Directory of Open Access Journals (Sweden)

    Elizabeth S. Fernandes

    2014-01-01

    Full Text Available Thousands of people suffer from severe malaria every year. The innate immune response plays a determinant role in host’s defence to malaria. Transient receptor potential vanilloid 1 (TRPV1 modulates macrophage-mediated responses in sepsis, but its role in other pathogenic diseases has never been addressed. We investigated the effects of capsazepine, a TRPV1 antagonist, in malaria. C57BL/6 mice received 105 red blood cells infected with Plasmodium berghei ANKA intraperitoneally. Noninfected mice were used as controls. Capsazepine or vehicle was given intraperitoneally for 6 days. Mice were culled on day 7 after infection and blood and spleen cell phenotype and activation were evaluated. Capsazepine decreased circulating but not spleen F4/80+Ly6G+ cell numbers as well as activation of both F4/80+and F4/80+Ly6G+ cells in infected animals. In addition, capsazepine increased circulating but not spleen GR1+ and natural killer (NK population, without interfering with natural killer T (NKT cell numbers and blood NK and NKT activation. However, capsazepine diminished CD69 expression in spleen NKT but not NK cells. Infection increased lipid peroxidation and the release of TNFα and IFNγ, although capsazepine-treated group exhibited lower levels of lipid peroxidation and TNFα. Capsazepine treatment did not affect parasitaemia. Overall, TRPV1 antagonism modulates the innate immune response to malaria.

  4. Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling.

    Science.gov (United States)

    Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

    2016-01-01

    High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na(+) channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

  5. Felbamate antagonizes isoniazid- and FG 7142-induced reduction of GABAA receptor function in mouse brain.

    Science.gov (United States)

    Serra, M; Ghiani, C A; Spano, S; Biggio, G

    1994-11-24

    Injection of the antiepileptic drug, felbamate (2-phenyl-1,3-propanediol dicarbamate), into mice reduced in a dose-dependent manner (150-300 mg/kg i.p.) the isoniazid (200 mg/kg s.c.)-induced increase in ex vivo binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) to cerebral cortical and hippocampal membranes. The same doses of felbamate reduced significantly the number of mice exhibiting isoniazid-induced seizures. A dose of felbamate (50 mg/kg) ineffective in isoniazid-treated mice completely antagonized the increase of [35S]TBPS binding elicited by FG 7142 (N-methyl-beta-carboline-3-carboxamide), a benzodiazepine receptor inverse agonist. The above effects of felbamate resembled those of diazepam. Accordingly, the combination of ineffective doses of felbamate (50 mg/kg) and diazepam (0.2 mg/kg) elicited a marked decrease of [35S]TBPS binding. The results indicate that facilitation of gamma-aminobutyric acid type A (GABAA) receptor function may play a role in the anticonvulsant action of felbamate. PMID:7875235

  6. Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation

    International Nuclear Information System (INIS)

    N-7 and 2′-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m7GpppN; cap 1, m7GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2′-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2′-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5′-end of viral RNA modulate host pathogen recognition responses to promote infection and disease

  7. Antagonism and Molecular Identification of an Antibiotic Bacterium BS04 Against Phytopathogenic Fungi and Bacteria

    Institute of Scientific and Technical Information of China (English)

    Xie Jing(谢晶); Ge Shaorong; Tao Yong; Gao Ping; Liu Kun; Liu Shigui

    2004-01-01

    Through a modified agar well diffusion assay, antagonism of bacterium BS04 is tested. The data show that BS04 has antibiotic activity against phytopathogenic fungi and bacteria, including Phoma wasabiae Yokogi, Cochlibolus Heterostrophu, Exserohilum Turcicum, Curuvularia Lunata (Walk) Boed, Thantephorus cucumris, Fusarium graminearum, Xanthomonas axonopodis pv. Citri (Hasse) Dye and Xanthomonas zingiberi (Uyeda) Savulescu. The products of bacterium BS04 can endure the treatment of a wide range of pH, and maintain the antibiotic activity after treatment of 100℃ for 30 min. The result suggests that bacterium BS04 has the potential as a promising biocontrol agent. In order to determine the taxonomic placement, the molecular identification of BS04 is performed. The comparative analysis of 16s rDNA sequences indicates that the 16s rDNA sequence of BS04 is highly homologous with sequences of typical Paenibacillus bacteria from the RPD library (from 92% to 99%). And the constructed phylogenetic tree by using maximum-likelihood method with Bootstrap Trial 1000 proves that BS04 is subjected to Paenibacillus polymyxa.

  8. Prolongevity medicine: Antagonic-Stress drug in distress, geriatrics, and related diseases. II. Clinical review--2003.

    Science.gov (United States)

    Riga, S; Riga, D; Schneider, F

    2004-06-01

    Distress and senescence, their reciprocal aggravating-quickening connections, and their related pathologies have a large worldwide impact on healthcare systems in this new millennium. For this reason, Antagonic-Stress (AS)--an advanced integrative therapy, with specific synergistic composition, and patented internationally--represents a significant strategy in health, aging, and longevity. Clinical research with AS proves the drug's efficacy in the management of distress (neurotic, stress-related, and affective disorders; behavioral syndromes associated with physiological disturbances and physical factors; mental and behavioral disorders due to psychoactive substance uses) and psychogeriatrics [organic, including symptomatic, mental disorders (OMD)]. Specific multiaxial psychopathological instruments and psychometric tests in multiple assessments used for gerontopsychiatry demonstrated strong improvements after AS administration in early-moderate stages of Alzheimer or vascular dementia, as well as in other OMD. In addition, comparative clinical studies evinced the superiority of AS (synergistic multitherapy) versus monotherapy [meclofenoxate (MF), piracetam (PA), pyritinol (PT), and nicergoline (NE), respectively]. These comparative clinical trials agreed closely with comparative preclinical research and confirmed AS synergistic homeostatic, adaptogenic, antioxidative, cerebrovascular, neurometabolic, and nootropic actions. Also, the AS protective actions against oxidative stress recommend this orthomolecular therapy in stress, aging, and free radical pathology. PMID:15247054

  9. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  10. ToxR Antagonizes H-NS Regulation of Horizontally Acquired Genes to Drive Host Colonization.

    Directory of Open Access Journals (Sweden)

    Misha I Kazi

    2016-04-01

    Full Text Available The virulence regulator ToxR initiates and coordinates gene expression needed by Vibrio cholerae to colonize the small intestine and cause disease. Despite its prominence in V. cholerae virulence, our understanding of the direct ToxR regulon is limited to four genes: toxT, ompT, ompU and ctxA. Here, we determine ToxR's genome-wide DNA-binding profile and demonstrate that ToxR is a global regulator of both progenitor genome-encoded genes and horizontally acquired islands that encode V. cholerae's major virulence factors and define pandemic lineages. We show that ToxR shares more than a third of its regulon with the histone-like nucleoid structuring protein H-NS, and antagonizes H-NS binding at shared binding locations. Importantly, we demonstrate that this regulatory interaction is the critical function of ToxR in V. cholerae colonization and biofilm formation. In the absence of H-NS, ToxR is no longer required for V. cholerae to colonize the infant mouse intestine or for robust biofilm formation. We further illustrate a dramatic difference in regulatory scope between ToxR and other prominent virulence regulators, despite similar predicted requirements for DNA binding. Our results suggest that factors in addition to primary DNA structure influence the ability of ToxR to recognize its target promoters.

  11. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation

    Institute of Scientific and Technical Information of China (English)

    Hai Jiang; Jianchun Wu; Chen He; Wending Yang; Honglin Li

    2009-01-01

    Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kB signaling. We report here the identification of C53 protein as a novel regulator of Cdk1 activation. We found that knockdown of C53 protein causes delayed Cdkl activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 (Chk1 and Chk2) is partially inhibited by C53 overexpression. Intriguingly, we found that C53 interacts with Chkl and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdk1 activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chk1, C53 promotes Cdk1 activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.

  12. How does the antagonism between capping and anti-capping proteins affect actin network dynamics?

    International Nuclear Information System (INIS)

    Actin-based cell motility is essential to many biological processes. We built a simplified, three-dimensional computational model and subsequently performed stochastic simulations to study the growth dynamics of lamellipodia-like branched networks. In this work, we shed light on the antagonism between capping and anti-capping proteins in regulating actin dynamics in the filamentous network. We discuss detailed mechanisms by which capping and anti-capping proteins affect the protrusion speed of the actin network and the rate of nucleation of filaments. We computed a phase diagram showing the regimes of motility enhancement and inhibition by these proteins. Our work shows that the effects of capping and anti-capping proteins are mainly transmitted by modulation of the filamentous network density and local availability of monomeric actin. We discovered that the combination of the capping/anti-capping regulatory network with nucleation-promoting proteins introduces robustness and redundancy in cell motility machinery, allowing the cell to easily achieve maximal protrusion speeds under a broader set of conditions. Finally, we discuss distributions of filament lengths under various conditions and speculate on their potential implication for the emergence of filopodia from the lamellipodial network.

  13. Cardiovascular and behavioral responses of gray wolves to ketamine-xylazine immobilization and antagonism by yohimbine

    Science.gov (United States)

    Kreeger, T.J.; Faggella, A.M.; Seal, U.S.; Mech, L.D.; Callahan, M.; Hall, B.

    1987-01-01

    Adult wolves (Canis lupus) were immobilized with 6.6 mg/kg ketamine hydrochloride (KET) and 2.2 mg/kg xylazine hydrochloride (XYL) administered intramuscularly. Induction time was 4.6 +/- 0.3 min (mean +/- SE). Immobilization resulted in significant bradycardia and hypertension (P less than 0.05). Twenty min after induction, the wolves were given 0.05-0.60 mg/kg yohimbine hydrochloride (YOH). Yohimbine given intravenously produced dose-related increases in heart rate (HR) with doses greater than 0.15 mg/kg resulting in extreme tachycardia (greater than 300 bpm). All doses of YOH caused a temporary decrease in mean arterial blood pressure (MABP) with some individual animals manifesting profound hypotension (less than 30 torr) at doses greater than 0.15 mg/kg. Increasing the dose of YOH above 0.15 mg/kg did not significantly decrease either arousal or ambulation times. Administering YOH at 40 or 60 min after induction resulted in decreased arousal and ambulation times. Stimulation by weighing and taking repeated blood samples during anesthesia did not shorten arousal times. We recommend that wolves immobilized with XYL-KET be antagonized with doses of YOH less than 0.15 mg/kg.

  14. Exploring the structural basis of mercury/selenium antagonism in green onion. Allium fistulosum

    International Nuclear Information System (INIS)

    Complete text of publication follows. While significant efforts have been devoted to deciphering the mutually protective effect of mercury and selenium in mammals, a limited number of studies have investigated the potential antagonism between mercury and selenium in plants, which may provide useful information for the purpose of phytoremediating mercury. In this study, the Allium fistulosum, green onion, was used to investigate the metabolic fate of mercury in conjunction with selenium. The plants were grown in perlite media and supplemented with sodium selenite and mercuric chloride. Data from x-ray fluorescence mapping of a freshly excised root and capillary reversed phase chromatography coupled with inductively coupled plasma mass spectrometry detection of homogenized root extract, suggest the plausible formation of a mercury-selenium species and a similarly structured mercury-sulfur species, predominantly residing in the cell wall of the epidermal root tissue. X-ray absorption fine structure spectroscopy was used to probe the local environment of mercury and selenium in order to help elucidate the varying metabolites. A putative molecular basis for the formation of the mercury-selenium species will be discussed.

  15. How does the antagonism between capping and anti-capping proteins affect actin network dynamics?

    Science.gov (United States)

    Hu, Longhua; Papoian, Garegin A.

    2011-09-01

    Actin-based cell motility is essential to many biological processes. We built a simplified, three-dimensional computational model and subsequently performed stochastic simulations to study the growth dynamics of lamellipodia-like branched networks. In this work, we shed light on the antagonism between capping and anti-capping proteins in regulating actin dynamics in the filamentous network. We discuss detailed mechanisms by which capping and anti-capping proteins affect the protrusion speed of the actin network and the rate of nucleation of filaments. We computed a phase diagram showing the regimes of motility enhancement and inhibition by these proteins. Our work shows that the effects of capping and anti-capping proteins are mainly transmitted by modulation of the filamentous network density and local availability of monomeric actin. We discovered that the combination of the capping/anti-capping regulatory network with nucleation-promoting proteins introduces robustness and redundancy in cell motility machinery, allowing the cell to easily achieve maximal protrusion speeds under a broader set of conditions. Finally, we discuss distributions of filament lengths under various conditions and speculate on their potential implication for the emergence of filopodia from the lamellipodial network.

  16. How does the antagonism between capping and anti-capping proteins affect actin network dynamics?

    Energy Technology Data Exchange (ETDEWEB)

    Hu Longhua; Papoian, Garegin A, E-mail: gpapoian@umd.edu [Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742 (United States)

    2011-09-21

    Actin-based cell motility is essential to many biological processes. We built a simplified, three-dimensional computational model and subsequently performed stochastic simulations to study the growth dynamics of lamellipodia-like branched networks. In this work, we shed light on the antagonism between capping and anti-capping proteins in regulating actin dynamics in the filamentous network. We discuss detailed mechanisms by which capping and anti-capping proteins affect the protrusion speed of the actin network and the rate of nucleation of filaments. We computed a phase diagram showing the regimes of motility enhancement and inhibition by these proteins. Our work shows that the effects of capping and anti-capping proteins are mainly transmitted by modulation of the filamentous network density and local availability of monomeric actin. We discovered that the combination of the capping/anti-capping regulatory network with nucleation-promoting proteins introduces robustness and redundancy in cell motility machinery, allowing the cell to easily achieve maximal protrusion speeds under a broader set of conditions. Finally, we discuss distributions of filament lengths under various conditions and speculate on their potential implication for the emergence of filopodia from the lamellipodial network.

  17. Coarse-grained quantum transport simulation for analyzing leakage-mobility antagonism in GNRFET

    Science.gov (United States)

    Ito, Masakatsu; Sato, Shintaro; Yokoyama, Naoki; Joachim, Christian; Green Nanoelectronics Center Team; CEMES-CNRS and Mana Satellite Collaboration

    2013-03-01

    Since it became clear that graphene transistors based on the classical MOSFET principle suffer from serious performance problems, researchers have explored new graphene device design using quantum transport simulations. A first-principle quantum transport simulation, however, still takes unaffordable computational cost to deal with a realistic size of graphene transistor (>104 atoms). This motivated us to import ESQC (elastic scattering quantum chemistry) technique from the research field of molecular electronics and to develop its coarse-grained version. To eliminate the atomic scale details, we reformulated ESQC technique using the continuum limit description of graphene charge carriers, which is given by the massless Dirac equation. Since the potential function in this Dirac equation is electrostatic potential distribution, it can be obtained from Poisson equation with the boundary conditions of gate voltages in a self-consistent manner. We are now applying this coarse-grained quantum transport simulation to GNRFETs (graphene nanoribbon field effect transistors) for resolving the mobility-leakage antagonism, where opening a bandgap in a graphene channel improves its switching ability but at the same time deteriorates the electron channel mobility.

  18. Conditions that Stabilize Membrane Domains Also Antagonize n-Alcohol Anesthesia

    Science.gov (United States)

    Machta, Benjamin B.; Gray, Ellyn; Nouri, Mariam; McCarthy, Nicola L. C.; Gray, Erin M.; Miller, Ann L.; Brooks, Nicholas J.; Veatch, Sarah L.

    2016-08-01

    Diverse molecules induce general anesthesia with potency strongly correlated both with their hydrophobicity and their effects on certain ion channels. We recently observed that several n-alcohol anesthetics inhibit heterogeneity in plasma membrane derived vesicles by lowering the critical temperature ($T_c$) for phase separation. Here we exploit conditions that stabilize membrane heterogeneity to further test the correlation between the anesthetic potency of n-alcohols and effects on $T_c$. First we show that hexadecanol acts oppositely to n-alcohol anesthetics on membrane mixing and antagonizes ethanol induced anesthesia in a tadpole behavioral assay. Second, we show that two previously described `intoxication reversers' raise $T_c$ and counter ethanol's effects in vesicles, mimicking the findings of previous electrophysiological and behavioral measurements. Third, we find that hydrostatic pressure, long known to reverse anesthesia, also raises $T_c$ in vesicles with a magnitude that counters the effect of butanol at relevant concentrations and pressures. Taken together, these results demonstrate that $\\Delta T_c$ predicts anesthetic potency for n-alcohols better than hydrophobicity in a range of contexts, supporting a mechanistic role for membrane heterogeneity in general anesthesia.

  19. Dopamine D2/3 receptor antagonism reduces activity-based anorexia.

    Science.gov (United States)

    Klenotich, S J; Ho, E V; McMurray, M S; Server, C H; Dulawa, S C

    2015-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by severe hypophagia and weight loss, and an intense fear of weight gain. Activity-based anorexia (ABA) refers to the weight loss, hypophagia and paradoxical hyperactivity that develops in rodents exposed to running wheels and restricted food access, and provides a model for aspects of AN. The atypical antipsychotic olanzapine was recently shown to reduce both AN symptoms and ABA. We examined which component of the complex pharmacological profile of olanzapine reduces ABA. Mice received 5-HT(2A/2C), 5-HT3, dopamine D1-like, D2, D3 or D2/3 antagonist treatment, and were assessed for food intake, body weight, wheel running and survival in ABA. D2/3 receptor antagonists eticlopride and amisulpride reduced weight loss and hypophagia, and increased survival during ABA. Furthermore, amisulpride produced larger reductions in weight loss and hypophagia than olanzapine. Treatment with either D3 receptor antagonist SB277011A or D2 receptor antagonist L-741,626 also increased survival. All the other treatments either had no effect or worsened ABA. Overall, selective antagonism of D2 and/or D3 receptors robustly reduces ABA. Studies investigating the mechanisms by which D2 and/or D3 receptors regulate ABA, and the efficacy for D2/3 and/or D3 antagonists to treat AN, are warranted. PMID:26241351

  20. Identification of proteins involved in Hg-Se antagonism in water hyacinth (Eichhornia crassipes).

    Science.gov (United States)

    Pacheco, Pablo; Hanley, Traci; Figueroa, Julio A Landero

    2014-03-01

    Different studies have established the presence of a proteinaceus complex involved in Hg-Se agonism/antagonism in plants. In order to identify proteins involved in this mechanism, water hyacinth plants were divided into groups and supplemented with Hg, Se and a Hg-Se mixture. Proteins involved were identified through a screening separation by SEC-ICPMS followed by SAX-ICPMS and then peptide mapping of selected fractions by nanoLC-ESI-ITMS(2). Determination of total metal concentration showed that Se inhibits Hg translocation from roots to aerial compartments of the plant and that Se and Hg are antagonists to each other in terms of plant toxicity. In roots, stems and leaves Se was distributed mainly in two molecular mass fractions water hyacinth were more evident in leaves in contrast to other compartments. Several proteins, possibly associated with either Se or Hg, were identified in roots, stems and leaves. Most of the identified proteins were associated with Hg and located in leaves, and these are associated specifically with chloroplast and mitochondria proteins, related to essential mechanisms in plants such as photosynthesis, carbon fixation and the electron transport chain. PMID:24352585

  1. Plant Essential Oils Synergize and Antagonize Toxicity of Different Conventional Insecticides against Myzus persicae (Hemiptera: Aphididae.

    Directory of Open Access Journals (Sweden)

    Nicoletta Faraone

    Full Text Available Plant-derived products can play an important role in pest management programs. Essential oils from Lavandula angustifolia (lavender and Thymus vulgaris (thyme and their main constituents, linalool and thymol, respectively, were evaluated for insecticidal activity and synergistic action in combination with insecticides against green peach aphid, Myzus persicae (Sulzer (Hemiptera: Aphididae. The essential oils and their main constituents exerted similar insecticidal activity when aphids were exposed by direct sprays, but were non-toxic by exposure to treated leaf discs. In synergism experiments, the toxicity of imidacloprid was synergized 16- to 20-fold by L. angustifolia and T. vulgaris essential oils, but far less synergism occurred with linalool and thymol, indicating that secondary constituents of the oils were probably responsible for the observed synergism. In contrast to results with imidacloprid, the insecticidal activity of spirotetramat was antagonized by L. angustifolia and T. vulgaris essential oils, and linalool and thymol. Our results demonstrate the potential of plant essential oils as synergists of insecticides, but show that antagonistic action against certain insecticides may occur.

  2. Synergism and antagonism in Iron base metallic glass corrosion inhibition by Thiosemicarbazone Compounds and Bromide Ions

    International Nuclear Information System (INIS)

    The synergistic and antagonism action caused by Br ions on the corrosion inhibition of fe78B13Si19 glassy alloy in 0.2 M Na2SO4 in absence and presence 10 (to power-4) M of some thiosemicarbazone derivatives have been investigated using potentiodynamic polarization, a.c. impedance techniques and morphological study. Results show that the addition of Br ions to sulphate solution inhibit the corrosion process by acting as an electron transfer barrier due to direct adsorption of these ions on alloy surface. A synergistic effect exists when fixed concentration of studied thiosemicarbazone derivatives and low concentration Br ions are used together to prevent glassy alloy corrosion in Na2SO4. The increase in surface coverage values in the presence at low concentrations Br ions indicates that an insoluble complex formed by undergoing a joint adsorption. The synergism parameter (S) is defined and calculated by the surface coverage values. The parameter in the case of small amount of Br found to be more than unity, indicating that the enhanced inhibition efficiency caused by the addition of Br ions is only due to synergism and there is a definite contribution from the inhibitor molecule. (author)

  3. Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity

    Science.gov (United States)

    Cheng, Pin-Nan; Liu, Cong; Zhao, Minglei; Eisenberg, David; Nowick, James S.

    2012-11-01

    The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β2-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles.

  4. Interferon alpha antagonizes STAT3 and SOCS3 signaling triggered by hepatitis C virus.

    Science.gov (United States)

    Zhao, Lan-Juan; He, Sheng-Fei; Wang, Wen; Ren, Hao; Qi, Zhong-Tian

    2016-04-01

    We aimed to investigate regulation of signal transducer and activator of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) by interferon alpha (IFN-α) and to analyze the relationship between STAT3 and SOCS3 during hepatitis C virus (HCV) infection. Changes in STAT3 and SOCS3 were analyzed at both mRNA and protein levels in human hepatoma cells infected with HCV (J6/JFH1). At 72h of HCV infection, STAT3 expression was decreased with sustained phosphorylation, and IFN-α increased such decrease and phosphorylation. HCV increased SOCS3 expression, while IFN-α impaired such increase, indicating different regulation of STAT3 and SOCS3 by IFN-α. IFN-α-induced expression and phosphorylation of upstream kinases of the JAK/STAT pathway, Tyk2 and Jak1, were suppressed by HCV. Moreover, knockdown of STAT3 by RNA interference led to decreases in HCV RNA replication and viral protein expression, without affecting either the expression of Tyk2 and Jak1 or the SOCS3 induction in response to IFN-α. These results show that IFN-α antagonizes STAT3 and SOCS3 signaling triggered by HCV and that STAT3 regulation correlates inversely with SOCS3 induction by IFN-α, which may be important in better understanding the complex interplay between IFN-α and signal molecules during HCV infection. PMID:26945996

  5. Evidence of pomegranate methanolic extract in antagonizing the endogenous SERM, 27-hydroxycholesterol.

    Science.gov (United States)

    Vini, Ravindran; Juberiya, Azeez M; Sreeja, Sreeharshan

    2016-02-01

    The direct relationship between obesity and breast cancer has been elucidated recently with the identification of a cholesterol derivative 27-hydroxycholesterol (27HC), an endogenous SERM that can act through estrogen receptor (ER)-mediated mechanisms. Our recent research shed light on the possible SERM-like property of methanol extract of pericarp of pomegranate (PME) by using human breast (MCF-7, MDA-MB-231), endometrial (HEC-1A), cervical (SiHa, HeLa), ovarian (SKOV3) cancer cell lines, normal breast fibroblasts (MCF-10A) and also by in vivo models (ovariectomized Swiss albino mice). Our findings demonstrated that PME binds to ER and downregulates the Estrogen response elements (ERE)-mediated transcription in breast cancer cells without being agonistic in the uterine endometrium and has cardioprotective effects comparable to that of 17-β-estradiol. This preliminary work indicates the ability of PME to antagonize the activity of 27HC. We hypothesize that PME can compete with 27HC for ERα and reduce 27HC-induced proliferation of MCF-7 cells. Relevant estrogen-regulated genes such as pS2, PR and ERα were checked to evaluate the ability of PME to abrogate 27HC-induced genes. This study is significant, being the first report describing that bioactive components of the methanolic extract of pericarp of PME, a proven SERM could plausibly compete for 27HC. PMID:26756990

  6. E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor

    International Nuclear Information System (INIS)

    Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4ORF3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4ORF3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins. - Highlights: • E1B-55K or E4orf3 prevents nuclear fragmentation. • Nuclear fragmentation requires AIF and PARP-1 activity. • Adenovirus DNA replication activates PARP-1. • E1B-55K or E4orf3 proteins alter the distribution of PAR

  7. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    International Nuclear Information System (INIS)

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN

  8. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats.

    Science.gov (United States)

    Gowen, M; Stroup, G B; Dodds, R A; James, I E; Votta, B J; Smith, B R; Bhatnagar, P K; Lago, A M; Callahan, J F; DelMar, E G; Miller, M A; Nemeth, E F; Fox, J

    2000-06-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a "calcilytic") of the parathyroid cell Ca(2+) receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17beta-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca(2+) receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  9. Salicylic acid antagonizes abscisic acid inhibition of shoot growth and cell cycle progression in rice

    Science.gov (United States)

    Meguro, Ayano; Sato, Yutaka

    2014-04-01

    We analysed effects of abscisic acid (ABA, a negative regulatory hormone), alone and in combination with positive or neutral hormones, including salicylic acid (SA), on rice growth and expression of cell cycle-related genes. ABA significantly inhibited shoot growth and induced expression of OsKRP4, OsKRP5, and OsKRP6. A yeast two-hybrid assay showed that OsKRP4, OsKRP5, and OsKRP6 interacted with OsCDKA;1 and/or OsCDKA;2. When SA was simultaneously supplied with ABA, the antagonistic effect of SA completely blocked ABA inhibition. SA also blocked ABA inhibition of DNA replication and thymidine incorporation in the shoot apical meristem. These results suggest that ABA arrests cell cycle progression by inducing expression of OsKRP4, OsKRP5, and OsKRP6, which inhibit the G1/S transition, and that SA antagonizes ABA by blocking expression of OsKRP genes.

  10. ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

    Science.gov (United States)

    Heybach, J. P.; Vernikos, J.

    1981-01-01

    The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.

  11. Effect of endothelin antagonism on the production of cytokines in eosinophilic airway inflammation.

    Science.gov (United States)

    Finsnes, F; Lyberg, T; Christensen, G; Skjønsberg, O H

    2001-04-01

    Endothelin (ET)-1 has been launched as an important mediator in bronchial asthma, which is an eosinophilic airway inflammation. However, the interplay between ET-1 and other proinflammatory mediators during the development of airway inflammation has not been elucidated. We wanted to study 1) whether the production of ET-1 precedes the production of other proinflammatory mediators and 2) whether ET-1 stimulates the production of these mediators within the airways. These hypotheses were studied during the development of an eosinophilic airway inflammation in rats. The increase in ET-1 mRNA level in lung tissue preceded the increase in mRNA levels of tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-8. Treatment of the animals with the ET receptor antagonist bosentan resulted in a substantial decrease in the concentrations of tumor necrosis factor-alpha, IL-4, IL-1beta, interferon-gamma, and ET-1 in bronchoalveolar lavage fluid. In conclusion, the synthesis of ET-1 as measured by increased mRNA level precedes the synthesis of other proinflammatory cytokines of importance for the development of an eosinophilic airway inflammation, and ET antagonism inhibits the production of these mediators within the airways. Whether treatment with ET antagonists will prove beneficial for patients with eosinophilic airway inflammations like bronchial asthma is not yet known. PMID:11238005

  12. E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor

    Energy Technology Data Exchange (ETDEWEB)

    Turner, Roberta L. [Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Wilkinson, John C., E-mail: john.wilkinson@ndsu.edu [Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Ornelles, David A., E-mail: ornelles@wakehealth.edu [Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States)

    2014-05-15

    Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4ORF3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4ORF3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins. - Highlights: • E1B-55K or E4orf3 prevents nuclear fragmentation. • Nuclear fragmentation requires AIF and PARP-1 activity. • Adenovirus DNA replication activates PARP-1. • E1B-55K or E4orf3 proteins alter the distribution of PAR.

  13. Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation

    Energy Technology Data Exchange (ETDEWEB)

    Hyde, Jennifer L. [Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110 (United States); Diamond, Michael S., E-mail: diamond@borcim.wustl.edu [Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110 (United States); Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110 (United States); Pathology & Immunology, Washington University School of Medicine, St Louis., MO 63110 (United States); The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis., MO 63110 (United States)

    2015-05-15

    N-7 and 2′-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m{sup 7}GpppN; cap 1, m{sup 7}GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2′-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2′-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5′-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.

  14. Cerebral, spinal and peripheral inhibition of gastrointestinal transit by PI017: differential antagonism by naloxonazine

    International Nuclear Information System (INIS)

    The authors were interested in characterizing the relative importance of central (cerebral, spinal) and peripheral opioid receptors in inhibition of gastrointestinal transit. The mu-receptor selective agonist, (NMePhe3,D-Pro4)morphiceptin (PL017), was evaluated for its effectiveness in slowing gastrointestinal transit after subcutaneous, intracerebroventricular (i.c.v.) or intrathecal (i.th.) administration when given alone or after pretreatment with naloxonazine, an irreversible mu1 selective opioid receptor antagonist. Male, ICR mice (20-25 g) were pretreated with saline, naloxone or naloxonazine (35 mg/kg, s.c.) 25 hr prior to testing. Gastrointestinal transit was evaluated in previously fasted (18 hr) mice by oral administration of a liquid radiolabelled marker (Na251CrO4). I.th. PL017 (100-1000 ng) was effective in slowing transit, but was essentially insensitive to naloxone or naloxonazine pretreatment. PL017 produced a dose-related inhibition of transit when given by either the i.c.v. (100-1000 ng) or s.c.(1-10 mg/kg) route; this effect was not sensitive to naloxone pretreatment but was antagonized by naloxonazine. These results indicate that the opioid receptors mediating gastrointestinal transit in the brain and periphery may be mu1. In contrast, the insensitivity to naloxonazine suggests that the gastrointestinal effects of PL017 in the spinal cord may be the result of activation of mu2 or possibly delta opioid receptors

  15. Toxicities of glyphosate- and cypermethrin-based pesticides are antagonic in the tenspotted livebearer fish (Cnesterodon decemmaculatus).

    Science.gov (United States)

    Brodeur, Julie Céline; Malpel, Solène; Anglesio, Ana Belén; Cristos, Diego; D'Andrea, María Florencia; Poliserpi, María Belén

    2016-07-01

    Although pesticide contamination of surface waters normally occurs in the form of mixtures, the toxicity and interactions displayed by such mixtures have been little characterized until now. The present study examined the interactions prevailing in equitoxic and non-equitoxic binary mixtures of formulations of glyphosate (Glifoglex(®)) and cypermethrin (Glextrin(®)) to the tenspotted livebearer (Cnesterodon decemmaculatus), a widely distributed South American fish. The following 96 h-LC50s were obtained when pesticide formulations were tested individually: Glifoglex(®) 41.4 and 53 mg ae glyphosate/L; Glextrin(®) 1.89 and 2.60 μg cypermethrin/L. Equitoxic and non-equitoxic mixtures were significantly antagonic in all combinations tested. The magnitude of the antagonism (factor by which toxicity differed from concentration addition) varied between 1.37 and 3.09 times in the different non-equitoxic mixtures tested. Antagonism was due to a strong inhibition of cypermethrin toxicity by the glyphosate formulation, the toxicity of the cypermethrin-based pesticide being almost completely overridden by the glyphosate formulation. Results obtained in the current study with fish are radically opposite to those previously observed in tadpoles where synergy was observed when Glifoglex(®) and Glextrin(®) were present in mixtures (Brodeur et al., 2014). PMID:27139121

  16. Antagonism of Nav channels and α1-adrenergic receptors contributes to vascular smooth muscle effects of ranolazine.

    Science.gov (United States)

    Virsolvy, Anne; Farah, Charlotte; Pertuit, Nolwenn; Kong, Lingyan; Lacampagne, Alain; Reboul, Cyril; Aimond, Franck; Richard, Sylvain

    2015-01-01

    Ranolazine is a recently developed drug used for the treatment of patients with chronic stable angina. It is a selective inhibitor of the persistent cardiac Na(+) current (INa), and is known to reduce the Na(+)-dependent Ca(2+) overload that occurs in cardiomyocytes during ischemia. Vascular effects of ranolazine, such as vasorelaxation,have been reported and may involve multiple pathways. As voltage-gated Na(+) channels (Nav) present in arteries play a role in contraction, we hypothesized that ranolazine could target these channels. We studied the effects of ranolazine in vitro on cultured aortic smooth muscle cells (SMC) and ex vivo on rat aortas in conditions known to specifically activate or promote INa. We observed that in the presence of the Nav channel agonist veratridine, ranolazine inhibited INa and intracellular Ca(2+) calcium increase in SMC, and arterial vasoconstriction. In arterial SMC, ranolazine inhibited the activity of tetrodotoxin-sensitive voltage-gated Nav channels and thus antagonized contraction promoted by low KCl depolarization. Furthermore, the vasorelaxant effects of ranolazine, also observed in human arteries and independent of the endothelium, involved antagonization of the α1-adrenergic receptor. Combined α1-adrenergic antagonization and inhibition of SMCs Nav channels could be involved in the vascular effects of ranolazine. PMID:26655634

  17. Silencing Huntington's chorea: Is RNA Interference a Potential Cure?

    Directory of Open Access Journals (Sweden)

    Gerlinde A. Metz

    2006-01-01

    Full Text Available In 1872, George Huntington described Huntington's disease as characterized by motor, cognitive and psychiatric impairments. Huntington's disease is a dominant and autosomal mutation on chromosome 4 featuring the insertion of numerous CAG repeats. CAG codes for the amino acid, glutmanine that forms part of the Huntingtin protein (htt. Excess glutamine attachments make htt prone to accumulate in neurons. Three genes can be considered when developing therapies for Huntington's disease. They include targeting the symptoms of the disease, the progression of the disease and the cause of the disease. By using RNA interference (RNAi, the cause of the disease can be targeted. RNAi is a method that could potentially silence the formation of abnormal htt. This paper will discuss how RNAi could potentially cure Huntington's disease, by describing the genetic and proteinomic basis of Huntington's disease, the function of RNAi in Huntington's disease and the problems of benefits of RNAi. Preliminary work using RNAi in transgenic mice has shown a decrease in the behavioural expression of the mutant Huntington gene. There are several limitations associated with using RNAi as a gene therapy. For example, the effects of RNAi are short lived. A transposition system such as Sleeping Beauty can be used to increase the integration of the gene, however, for patients who currently have Huntington's disease, RNAi may potentially be used in combination with drugs or other treatments to target both symptoms and the underlying cause of Huntington's disease. This combination could eventually alleviate many painful symptoms associated with Huntington's disease and could even stop the progressive neurodegeneration of Huntington's disease. This review concludes that a substantial amount of new research is still necessary before RNAi is directly applicable to human patients with Huntington's disease.

  18. Tumor Selective Silencing Using an RNAi-Conjugated Polymeric Nanopharmaceutical.

    Science.gov (United States)

    Svenson, Sonke; Case, Roy I; Cole, Roderick O; Hwang, Jungyeon; Kabir, Sujan R; Lazarus, Douglas; Lim Soo, Patrick; Ng, Pei-Sze; Peters, Christian; Shum, Pochi; Sweryda-Krawiec, Beata; Tripathi, Snehlata; van der Poll, Derek; Eliasof, Scott

    2016-03-01

    Small interfering RNA (siRNA) therapeutics have potential advantages over traditional small molecule drugs such as high specificity and the ability to inhibit otherwise "undruggable" targets. However, siRNAs have short plasma half-lives in vivo, can induce a cytokine response, and show poor cellular uptake. Formulating siRNA into nanoparticles offers two advantages: enhanced siRNA stability against nuclease degradation beyond what chemical modification alone can provide; and improved site-specific delivery that takes advantage of the enhanced permeability and retention (EPR) effect. Existing delivery systems generally suffer from poor delivery to tumors. Here we describe the formation and biological activity of polymeric nanopharmaceuticals (PNPs) based on biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) conjugated to siRNA via an intracellular cleavable disulfide linker (PLGA-siRNA). Additionally, these PNPs contain (1) PLGA conjugated to polyethylene glycol (PEG) for enhanced pharmacokinetics of the nanocarrier; (2) a cation for complexation of siRNA and charge compensation to avoid high negative zeta potential; and (3) neutral poly(vinyl alcohol) (PVA) to stabilize the PNPs and support the PEG shell to prevent particle aggregation and protein adsorption. The biological data demonstrate that these PNPs achieve prolonged circulation, tumor accumulation that is uniform throughout the tumor, and prolonged tumor-specific knockdown. PNPs employed in this study had no effect on body weight, blood cell count, serum chemistry, or cytokine response at doses >10 times the effective dose. PNPs, therefore, constitute a promising solution for achieving durable siRNA delivery and gene silencing in tumors. PMID:26835715

  19. Evidence for large complex networks of plant short silencing RNAs.

    Directory of Open Access Journals (Sweden)

    Daniel MacLean

    Full Text Available BACKGROUND: In plants and animals there are many classes of short RNAs that carry out a wide range of functions within the cell; short silencing RNAs (ssRNAs of 21-25 nucleotides in length are produced from double-stranded RNA precursors by the protein Dicer and guide nucleases and other proteins to their RNA targets through base pairing interactions. The consequence of this process is degradation of the targeted RNA, suppression of its translation or initiation of secondary ssRNA production. The secondary ssRNAs in turn could then initiate further layers of ssRNA production to form extensive cascades and networks of interacting RNA [1]. Previous empirical analysis in plants established the existence of small secondary ssRNA cascade [2], in which a single instance of this event occurred but it was not known whether there are other more extensive networks of secondary sRNA production. METHODOLOGY/PRINCIPAL FINDINGS: We generated a network by predicting targets of ssRNA populations obtained from high-throughput sequencing experiments. The topology of the network shows it to have power law connectivity distribution, to be dissortative, highly clustered and composed of multiple components. We also identify protein families, PPR and ULP1, that act as hubs within the network. Comparison of the repetition of genomic sub-sequences of ssRNA length between Arabidopsis and E.coli suggest that the network structure is made possible by the underlying repetitiveness in the genome sequence. CONCLUSIONS/SIGNIFICANCE: Together our results provide good evidence for the existence of a large, robust ssRNA interaction network with distinct regulatory function. Such a network could have a massive effect on the regulation of gene expression via mediation of transcript levels.

  20. ANTAGONISM OF A. VIRIDANS TO CONDITIONALLY - PATHOGENIC MICROFLORA OF THE NOSE AND OROPHARYNX OF CHILDREN WITH CARDIAC PATOLOGY

    Directory of Open Access Journals (Sweden)

    Stepansky D.O.

    2015-12-01

    Full Text Available Introduction. Search for harmless and simultaneously effective probiotics, which could be successfully used for treatment and prevention of infectious deseases, is currently important. A. viridans is of particular interest, as it is representative of the normal microflora of human with broad spectrum of antibacterial action. The use of this microorganism has a number of advantages: the absence of side effects on the body; high adhesive abilities; resistance to lysozyme in saliva; the ability of use in patients, sensitized to antibiotics and chemotherapeutic drugs; stimulation effects on the human immune system. Material and methods. The purpose of the study was to investigate the antagonism of A. viridans № 167 and autostrains of aerococcuses, isolated at patients, to conditionally - pathogenic microflora of the nose and oropharynx of children with cardiac patology. At the first stage of the study the microflora of the of the nose and oropharynx of 2 investigated categories was examined – 40 children 4-14 years with cardiac patology and 40 healthy children 4-5 years old. The second stage of work was to study the effect of A. viridans on the explored strains. Results and discussion. A. viridans manifests the antagonism to all studied strains of gram-positive and gram-negative microorganisms, except C. albisans. A. viridans antagonistic activity to staphylococci (10 + 3 mm and streptococci (10 + 2mm is at the approximately same level. It is interesting to compare the antagonism of aerococcuses to clinical isolates of S. pyogenes and similar strains from carriers (healthy children category. Impact of aerococcuses on P. mirabilis strain appeared at the highest level. Autosimbionts of A. viridans, isolated from healthy children, are more antagonistic to CPM strains, isolated from these children, than autostrains of A. viridans, isolated from children with with cardiac patology, and higher than the museum strain of A. viridans № 167 antagonism

  1. Repressor element-1 silencing transcription factor/neuronal restrictive silencer factor (REST/NRSF can regulate HSV-1 immediate-early transcription via histone modification

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    Hill James M

    2007-06-01

    Full Text Available Abstract Background During primary infection of its human host, Herpes Simplex Virus Type-1 (HSV-1 establishes latency in neurons where the viral genome is maintained in a circular form associated with nucleosomes in a chromatin configration. During latency, most viral genes are silenced, although the molecular mechanisms responsible for this are unclear. We hypothesized that neuronal factors repress HSV-1 gene expression during latency. A search of the HSV-1 DNA sequence for potential regulatory elements identified a Repressor Element-1/Neuronal Restrictive Silencer Element (RE-1/NRSE located between HSV-1 genes ICP22 and ICP4. We predicted that the Repressor Element Silencing Transcription Factor/Neuronal Restrictive Silencer Factor (REST/NRSF regulates expression of ICP22 and ICP4. Results Transient cotransfection indicated that REST/NRSF inhibited the activity of both promoters. In contrast, cotransfection of a mutant form of REST/NRSF encoding only the DNA-binding domain of the protein resulted in less inhibition. Stably transformed cell lines containing episomal reporter plasmids with a chromatin structure showed that REST/NRSF specifically inhibited the ICP4 promoter, but not the ICP22 promoter. REST/NRSF inhibition of the ICP4 promoter was reversed by histone deacetylase (HDAC inhibitor Trichostatin A (TSA. Additionally, chromatin immuno-precipitation (ChIP assays indicated that the corepressor CoREST was recruited to the proximity of ICP4 promoter and that acetylation of histone H4 was reduced in the presence of REST/NRSF. Conclusion Since the ICP4 protein is a key transactivator of HSV-1 lytic cycle genes, these results suggest that REST/NRSF may have an important role in the establishment and/or maintenance of HSV-1 gene silencing during latency by targeting ICP4 expression.

  2. Specific tandem repeats are sufficient for paramutation-induced trans-generational silencing.

    Directory of Open Access Journals (Sweden)

    Christiane L Belele

    Full Text Available Paramutation is a well-studied epigenetic phenomenon in which trans communication between two different alleles leads to meiotically heritable transcriptional silencing of one of the alleles. Paramutation at the b1 locus involves RNA-mediated transcriptional silencing and requires specific tandem repeats that generate siRNAs. This study addressed three important questions: 1 are the tandem repeats sufficient for paramutation, 2 do they need to be in an allelic position to mediate paramutation, and 3 is there an association between the ability to mediate paramutation and repeat DNA methylation levels? Paramutation was achieved using multiple transgenes containing the b1 tandem repeats, including events with tandem repeats of only one half of the repeat unit (413 bp, demonstrating that these sequences are sufficient for paramutation and an allelic position is not required for the repeats to communicate. Furthermore, the transgenic tandem repeats increased the expression of a reporter gene in maize, demonstrating the repeats contain transcriptional regulatory sequences. Transgene-mediated paramutation required the mediator of paramutation1 gene, which is necessary for endogenous paramutation, suggesting endogenous and transgene-mediated paramutation both require an RNA-mediated transcriptional silencing pathway. While all tested repeat transgenes produced small interfering RNAs (siRNAs, not all transgenes induced paramutation suggesting that, as with endogenous alleles, siRNA production is not sufficient for paramutation. The repeat transgene-induced silencing was less efficiently transmitted than silencing induced by the repeats of endogenous b1 alleles, which is always 100% efficient. The variability in the strength of the repeat transgene-induced silencing enabled testing whether the extent of DNA methylation within the repeats correlated with differences in efficiency of paramutation. Transgene-induced paramutation does not require extensive

  3. Development of a gene silencing DNA vector derived from a broad host range geminivirus

    Directory of Open Access Journals (Sweden)

    Hancock Leandria C

    2009-07-01

    Full Text Available Abstract Background Gene silencing is proving to be a powerful tool for genetic, developmental, and physiological analyses. The use of viral induced gene silencing (VIGS offers advantages to transgenic approaches as it can be potentially applied to non-model systems for which transgenic techniques are not readily available. However, many VIGS vectors are derived from Gemini viruses that have limited host ranges. We present a new, unipartite vector that is derived from a curtovirus that has a broad host range and will be amenable to use in many non-model systems. Results The construction of a gene silencing vector derived from the geminivirus Beet curly top virus (BCTV, named pWSRi, is reported. Two versions of the vector have been developed to allow application by biolistic techniques or by agro-infiltration. We demonstrate its ability to silence nuclear genes including ribulose bisphosphate carboxylase small subunit (rbcS, transketolase, the sulfur allele of magnesium chelatase (ChlI, and two homeotic transcription factors in spinach or tomato by generating gene-specific knock-down phenotypes. Onset of phenotypes occurred 3 to 12 weeks post-inoculation, depending on the target gene, in organs that developed after the application. The vector lacks movement genes and we found no evidence for significant spread from the site of inoculation. However, viral amplification in inoculated tissue was detected and is necessary for systemic silencing, suggesting that signals generated from active viral replicons are efficiently transported within the plant. Conclusion The unique properties of the pWSRi vector, the ability to silence genes in meristem tissue, the separation of virus and silencing phenotypes, and the broad natural host range of BCTV, suggest that it will have wide utility.

  4. Functional genomic analysis of cotton genes with agrobacterium-mediated virus-induced gene silencing.

    Science.gov (United States)

    Gao, Xiquan; Shan, Libo

    2013-01-01

    Cotton (Gossypium spp.) is one of the most agronomically important crops worldwide for its unique textile fiber production and serving as food and feed stock. Molecular breeding and genetic engineering of useful genes into cotton have emerged as advanced approaches to improve cotton yield, fiber quality, and resistance to various stresses. However, the understanding of gene functions and regulations in cotton is largely hindered by the limited molecular and biochemical tools. Here, we describe the method of an Agrobacterium infiltration-based virus-induced gene silencing (VIGS) assay to transiently silence endogenous genes in cotton at 2-week-old seedling stage. The genes of interest could be readily silenced with a consistently high efficiency. To monitor gene silencing efficiency, we have cloned cotton GrCla1 from G. raimondii, a homolog gene of Arabidopsis Cloroplastos alterados 1 (AtCla1) involved in chloroplast development, and inserted into a tobacco rattle virus (TRV) binary vector pYL156. Silencing of GrCla1 results in albino phenotype on the newly emerging leaves, serving as a visual marker for silencing efficiency. To further explore the possibility of using VIGS assay to reveal the essential genes mediating disease resistance to Verticillium dahliae, a fungal pathogen causing severe Verticillium wilt in cotton, we developed a seedling infection assay to inoculate cotton seedlings when the genes of interest are silenced by VIGS. The method we describe here could be further explored for functional genomic analysis of cotton genes involved in development and various biotic and abiotic stresses. PMID:23386302

  5. Development of RNA Interference Trigger-Mediated Gene Silencing in Entamoeba invadens.

    Science.gov (United States)

    Suresh, Susmitha; Ehrenkaufer, Gretchen; Zhang, Hanbang; Singh, Upinder

    2016-04-01

    Entamoeba histolytica, a protozoan parasite, is an important human pathogen and a leading parasitic cause of death. The organism has two life cycle stages, trophozoites, which are responsible for tissue invasion, and cysts, which are involved in pathogen transmission. Entamoeba invadens is the model system to study Entamoeba developmental biology, as high-grade regulated encystation and excystation are readily achievable. However, the lack of gene-silencing tools in E. invadens has limited the molecular studies that can be performed. Using the endogenous RNA interference (RNAi) pathway in Entamoeba, we developed an RNAi-based trigger gene-silencing approach inE. invadens We demonstrate that a gene's coding region that has abundant antisense small RNAs (sRNAs) can trigger silencing of a gene that is fused to it. The trigger fusion leads to the generation of abundant antisense sRNAs that map to the target gene, with silencing occurring independently of trigger location at the 5' or 3' end of a gene. Gene silencing is stably maintained during development, including encystation and excystation. We have used this approach to successfully silence two E. invadens genes: a putative rhomboid protease gene and a SHAQKY family Myb gene. The Myb gene is upregulated during oxidative stress and development, and its downregulation led, as predicted, to decreased viability under oxidative stress and decreased cyst formation. Thus, the RNAi trigger silencing method can be used to successfully investigate the molecular functions of genes inE. invadens Dissection of the molecular basis of Entamoeba stage conversion is now possible, representing an important technical advance for the system. PMID:26787723

  6. Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2

    OpenAIRE

    Jing Chen; Xibao Shi; Xiaozhuan Zhang; Li Wang; Jun Luo; Guangxu Xing; Ruiguang Deng; Hong Yang; Jinting Li; Aiping Wang; Gaiping Zhang

    2015-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host’s immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral infection. Here, we report for the first time the interaction between PRRSV and RNA silencing in both the porcine macrophages and African green monkey kidney cell line (MARC-145) cell line, which we...

  7. Organ-specific alterations in tobacco transcriptome caused by the PVX-derived P25 silencing suppressor transgene

    OpenAIRE

    Jada Balaji; Soitamo Arto J; Lehto Kirsi

    2013-01-01

    Abstract Background RNA silencing affects a broad range of regulatory processes in all eukaryotes ranging from chromatin structure maintenance to transcriptional and translational regulation and longevity of the mRNAs. Particularly in plants, it functions as the major defense mechanism against viruses. To counter-act this defense, plant viruses produce suppressors of RNA silencing (Viral suppressors of RNA silencing, VSRSs), which are essential for viruses to invade their specific host plants...

  8. HIV-1 Tat RNA silencing suppressor activity is conserved across kingdoms and counteracts translational repression of HIV-1

    OpenAIRE

    Qian, Shuiming; Zhong, Xuehua; Yu, Lianbo; Ding, Biao; Haan, Peter; Boris-Lawrie, Kathleen

    2009-01-01

    The RNA silencing pathway is an intracellular innate response to virus infections and retro-transposons. Many plant viruses counter this host restriction by RNA silencing suppressor (RSS) activity of a double-stranded RNA-binding protein, e.g., tomato bushy stunt virus P19. Here, we demonstrate P19 and HIV-1 Tat function across the plant and animal kingdoms and suppress a common step in RNA silencing that is downstream of small RNA maturation. Our experiments reveal that RNA silencing in HIV-...

  9. MafB antagonizes phenotypic alteration induced by GM-CSF in microglia

    Energy Technology Data Exchange (ETDEWEB)

    Koshida, Ryusuke, E-mail: rkoshida-myz@umin.ac.jp; Oishi, Hisashi, E-mail: hoishi@md.tsukuba.ac.jp; Hamada, Michito; Takahashi, Satoru

    2015-07-17

    Microglia are tissue-resident macrophages which are distributed throughout the central nervous system (CNS). Recent studies suggest that microglia are a unique myeloid population distinct from peripheral macrophages in terms of origin and gene expression signature. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic cytokine regulating myeloid development, has been shown to stimulate proliferation and alter phenotype of microglia in vitro. However, how its signaling is modulated in microglia is poorly characterized. MafB, a bZip transcriptional factor, is highly expressed in monocyte-macrophage lineage cells including microglia, although its role in microglia is largely unknown. We investigated the crosstalk between GM-CSF signaling and MafB by analyzing primary microglia. We found that Mafb-deficient microglia grew more rapidly than wild-type microglia in response to GM-CSF. Moreover, the expression of genes associated with microglial differentiation was more downregulated in Mafb-deficient microglia cultured with GM-CSF. Notably, such differences between the genotypes were not observed in the presence of M-CSF. In addition, we found that Mafb-deficient microglia cultured with GM-CSF barely extended their membrane protrusions, probably due to abnormal activation of RhoA, a key regulator of cytoskeletal remodeling. Altogether, our study reveals that MafB is a negative regulator of GM-CSF signaling in microglia. These findings could provide new insight into the modulation of cytokine signaling by transcription factors in microglia. - Highlights: • GM-CSF alters the phenotype of microglia in vitro more potently than M-CSF. • Transcription factor MafB antagonizes the effect of GM-CSF on microglia in vitro. • MafB deficiency leads to RhoA activation in microglia in response to GM-CSF. • We show for the first time the function of MafB in microglia.

  10. MafB antagonizes phenotypic alteration induced by GM-CSF in microglia

    International Nuclear Information System (INIS)

    Microglia are tissue-resident macrophages which are distributed throughout the central nervous system (CNS). Recent studies suggest that microglia are a unique myeloid population distinct from peripheral macrophages in terms of origin and gene expression signature. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic cytokine regulating myeloid development, has been shown to stimulate proliferation and alter phenotype of microglia in vitro. However, how its signaling is modulated in microglia is poorly characterized. MafB, a bZip transcriptional factor, is highly expressed in monocyte-macrophage lineage cells including microglia, although its role in microglia is largely unknown. We investigated the crosstalk between GM-CSF signaling and MafB by analyzing primary microglia. We found that Mafb-deficient microglia grew more rapidly than wild-type microglia in response to GM-CSF. Moreover, the expression of genes associated with microglial differentiation was more downregulated in Mafb-deficient microglia cultured with GM-CSF. Notably, such differences between the genotypes were not observed in the presence of M-CSF. In addition, we found that Mafb-deficient microglia cultured with GM-CSF barely extended their membrane protrusions, probably due to abnormal activation of RhoA, a key regulator of cytoskeletal remodeling. Altogether, our study reveals that MafB is a negative regulator of GM-CSF signaling in microglia. These findings could provide new insight into the modulation of cytokine signaling by transcription factors in microglia. - Highlights: • GM-CSF alters the phenotype of microglia in vitro more potently than M-CSF. • Transcription factor MafB antagonizes the effect of GM-CSF on microglia in vitro. • MafB deficiency leads to RhoA activation in microglia in response to GM-CSF. • We show for the first time the function of MafB in microglia

  11. ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors.

    Science.gov (United States)

    Halasi, Marianna; Wang, Ming; Chavan, Tanmay S; Gaponenko, Vadim; Hay, Nissim; Gartel, Andrei L

    2013-09-01

    NAC (N-acetyl-L-cysteine) is commonly used to identify and test ROS (reactive oxygen species) inducers, and to inhibit ROS. In the present study, we identified inhibition of proteasome inhibitors as a novel activity of NAC. Both NAC and catalase, another known scavenger of ROS, similarly inhibited ROS levels and apoptosis associated with H₂O₂. However, only NAC, and not catalase or another ROS scavenger Trolox, was able to prevent effects linked to proteasome inhibition, such as protein stabilization, apoptosis and accumulation of ubiquitin conjugates. These observations suggest that NAC has a dual activity as an inhibitor of ROS and proteasome inhibitors. Recently, NAC was used as a ROS inhibitor to functionally characterize a novel anticancer compound, piperlongumine, leading to its description as a ROS inducer. In contrast, our own experiments showed that this compound depicts features of proteasome inhibitors including suppression of FOXM1 (Forkhead box protein M1), stabilization of cellular proteins, induction of ROS-independent apoptosis and enhanced accumulation of ubiquitin conjugates. In addition, NAC, but not catalase or Trolox, interfered with the activity of piperlongumine, further supporting that piperlongumine is a proteasome inhibitor. Most importantly, we showed that NAC, but not other ROS scavengers, directly binds to proteasome inhibitors. To our knowledge, NAC is the first known compound that directly interacts with and antagonizes the activity of proteasome inhibitors. Taken together, the findings of the present study suggest that, as a result of the dual nature of NAC, data interpretation might not be straightforward when NAC is utilized as an antioxidant to demonstrate ROS involvement in drug-induced apoptosis. PMID:23772801

  12. The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory & urological disorders

    Directory of Open Access Journals (Sweden)

    Anthony Ford

    2013-12-01

    Full Text Available A sensory role for ATP was proposed long before general acceptance of its extracellular role. ATP activates & sensitizes signal transmission at multiple sites along the sensory axis, across multiple synapses. P2X & P2Y receptors mediate ATP modulation of sensory pathways & participate in dysregulation, where ATP action directly on primary afferent neurons (PANs, linking receptive field to CNS, has received much attention. Many PANs, especially C-fibers, are activated by ATP, via P2X3-containing trimers. P2X3 knock-out mice & knock-down in rats led to reduced nocifensive activity & visceral reflexes, suggesting that antagonism may offer benefit in sensory disorders. Recently, drug-like P2X3 antagonists, active in a many inflammatory & visceral pain models, have emerged. Significantly, these compounds have no overt CNS action & are inactive versus acute nociception. Selectively targeting ATP sensitization of PANs may lead to therapies that block inappropriate chronic signals at their source, decreasing drivers of peripheral & central wind-up, yet leaving defensive nociceptive and brain functions unperturbed. This article reviews this evidence, focusing on how ATP sensitization of PANs in visceral “hollow” organs primes them to chronic discomfort, irritation & pain (symptoms as well as exacerbated autonomic reflexes (signs, & how the use of isolated organ-nerve preparations has revealed this mechanism. Urinary & airways systems share many features: dependence on continuous afferent traffic to brainstem centers to coordinate efferent autonomic outflow; loss of descending inhibitory influence in functional & sensory disorders; dependence on ATP in mediating sensory responses to diverse mechanical and chemical stimuli; a mechanistically overlapping array of existing medicines for pathological conditions. These similarities may also play out in terms of future treatment of signs & symptoms, in the potential for benefit of P2X3 antagonists.

  13. Agonism, Antagonism, and Inverse Agonism Bias at the Ghrelin Receptor Signaling.

    Science.gov (United States)

    M'Kadmi, Céline; Leyris, Jean-Philippe; Onfroy, Lauriane; Galés, Céline; Saulière, Aude; Gagne, Didier; Damian, Marjorie; Mary, Sophie; Maingot, Mathieu; Denoyelle, Séverine; Verdié, Pascal; Fehrentz, Jean-Alain; Martinez, Jean; Banères, Jean-Louis; Marie, Jacky

    2015-11-01

    The G protein-coupled receptor GHS-R1a mediates ghrelin-induced growth hormone secretion, food intake, and reward-seeking behaviors. GHS-R1a signals through Gq, Gi/o, G13, and arrestin. Biasing GHS-R1a signaling with specific ligands may lead to the development of more selective drugs to treat obesity or addiction with minimal side effects. To delineate ligand selectivity at GHS-R1a signaling, we analyzed in detail the efficacy of a panel of synthetic ligands activating the different pathways associated with GHS-R1a in HEK293T cells. Besides β-arrestin2 recruitment and ERK1/2 phosphorylation, we monitored activation of a large panel of G protein subtypes using a bioluminescence resonance energy transfer-based assay with G protein-activation biosensors. We first found that unlike full agonists, Gq partial agonists were unable to trigger β-arrestin2 recruitment and ERK1/2 phosphorylation. Using G protein-activation biosensors, we then demonstrated that ghrelin promoted activation of Gq, Gi1, Gi2, Gi3, Goa, Gob, and G13 but not Gs and G12. Besides, we identified some GHS-R1a ligands that preferentially activated Gq and antagonized ghrelin-mediated Gi/Go activation. Finally, we unambiguously demonstrated that in addition to Gq, GHS-R1a also promoted constitutive activation of G13. Importantly, we identified some ligands that were selective inverse agonists toward Gq but not of G13. This demonstrates that bias at GHS-R1a signaling can occur not only with regard to agonism but also to inverse agonism. Our data, combined with other in vivo studies, may facilitate the design of drugs selectively targeting individual signaling pathways to treat only the therapeutically relevant function. PMID:26363071

  14. Differential effects of prednisone and growth hormone on fuel metabolism and insulin antagonism in humans

    International Nuclear Information System (INIS)

    Human growth hormone (hGH) and prednisone cause insulin resistance and glucose intolerance. However, it is unknown whether hGH and prednisone antagonize insulin action on protein, fat, and carbohydrate metabolism by a common or independent mechanism. Therefore, protein, fat, and carbohydrate metabolism was assessed simultaneously in four groups of eight subjects each after 7 days of placebo, recombinant DNA hGH (rhGH; 0.1 mg.kg-1.day-1), prednisone (0.8 mg.kg-1.day-1), or rhGH and prednisone administration after an 18-h fast and during gut infusion of glucose and amino acids (fed state). Fasting plasma glucose concentrations were similar during placebo and rhGH but elevated (P less than 0.001) during combined treatment, whereas plasma insulin concentrations were higher (237 +/- 57 pmol/ml, P less than 0.001) during combined than during placebo, rhGH, or prednisone treatment (34, 52, and 91 pM, respectively). In the fed state, plasma glucose concentrations were elevated only during combined treatment (11.3 +/- 2.1 mM, P less than 0.001). Plasma insulin concentrations were elevated during therapy with prednisone alone and rhGH alone (667 +/- 72 and 564 +/- 65 pmol/ml, respectively, P less than 0.001) compared with placebo (226 +/- 44 pmol/ml) but lower than with the combined rhGH and prednisone treatment (1249 +/- 54 pmol/ml, P less than 0.01). Protein oxidation 14C leucine increased (P less than 0.001) with prednisone therapy, decreased (P less than 0.001) with rhGH treatment, and was normal during the combined treatment

  15. Dynamics of bounded confidence opinion in heterogeneous social networks: Concord against partial antagonism

    Science.gov (United States)

    Kurmyshev, Evguenii; Juárez, Héctor A.; González-Silva, Ricardo A.

    2011-08-01

    Bounded confidence models of opinion dynamics in social networks have been actively studied in recent years, in particular, opinion formation and extremism propagation along with other aspects of social dynamics. In this work, after an analysis of limitations of the Deffuant-Weisbuch (DW) bounded confidence, relative agreement model, we propose the mixed model that takes into account two psychological types of individuals. Concord agents (C-agents) are friendly people; they interact in a way that their opinions always get closer. Agents of the other psychological type show partial antagonism in their interaction (PA-agents). Opinion dynamics in heterogeneous social groups, consisting of agents of the two types, was studied on different social networks: Erdös-Rényi random graphs, small-world networks and complete graphs. Limit cases of the mixed model, pure C- and PA-societies, were also studied. We found that group opinion formation is, qualitatively, almost independent of the topology of networks used in this work. Opinion fragmentation, polarization and consensus are observed in the mixed model at different proportions of PA- and C-agents, depending on the value of initial opinion tolerance of agents. As for the opinion formation and arising of “dissidents”, the opinion dynamics of the C-agents society was found to be similar to that of the DW model, except for the rate of opinion convergence. Nevertheless, mixed societies showed dynamics and bifurcation patterns notably different to those of the DW model. The influence of biased initial conditions over opinion formation in heterogeneous social groups was also studied versus the initial value of opinion uncertainty, varying the proportion of the PA- to C-agents. Bifurcation diagrams showed an impressive evolution of collective opinion, in particular, radical changes of left to right consensus or vice versa at an opinion uncertainty value equal to 0.7 in the model with the PA/C mixture of population near 50/50.

  16. Reversal of acute experimental cerebral vasospasm by calcium antagonism with verapamil.

    Science.gov (United States)

    Leblanc, R; Feindel, W; Yamamoto, L; Milton, J G; Frojmovic, M M

    1984-02-01

    Acute vasospasm of the transclivally exposed basilar artery of anesthetised cats was produced by the subarachnoid injection of platelet-rich plasma (PRP) treated with enough adenosine diphosphate (ADP) to induce platelet aggregation and secretion. Vasorelaxation was produced by the topical application of the calcium antagonist verapamil. Changes in the internal diameter of the basilar artery were determined by measuring the blood column diameter from photomicrographs taken sequentially, at 5 minute intervals, through the operating microscope. Changes in blood vessel diameter are expressed as a plus or minus percentage of the pretreatment diameter. Arterial blood pressure and blood gas values were kept in the physiological range for the cat. The subarachnoid injection of PRP-ADP produced severe constriction of the basilar artery (mean constriction at 5 minutes after injection: -40.7% +/- 2.8 SEM). Platelet-free plasma, ADP alone and Elliott's A solution had no spasmogenic effect when injected into the subarachnoid space. The topical application of the calcium channel blocker verapamil (0.1 mg per kg) 30 minutes after the injection of PRP-ADP, with the basilar artery still in spasm (mean constriction: -23% +/- 3.5 SEM), produced prompt and dramatic vasodilation (mean dilation at 5 minutes after application: +52.7% +/- 18.1 SEM). This spasmolytic effect persisted in a decremental fashion for the 60 minute period of observation, by which time the previously constricted vessel had returned to its normal size. These observations indicate that the platelet fraction of whole blood may be involved in the genesis of acute vasospasm following subarachnoid hemmorrhage and that this phenomenon can be readily reversed by calcium antagonism. PMID:6704793

  17. Copper Induces Vasorelaxation and Antagonizes Noradrenaline -Induced Vasoconstriction in Rat Mesenteric Artery

    Directory of Open Access Journals (Sweden)

    Yu-Chun Wang

    2013-11-01

    Full Text Available Background/Aims: Copper is an essential trace element for normal cellular function and contributes to critical physiological or pathological processes. The aim of the study was to investigate the effects of copper on vascular tone of rat mesenteric artery and compare the effects of copper on noradrenaline (NA and high K+ induced vasoconstriction. Methods: The rat mesenteric arteries were isolated and the vessel tone was measured by using multi wire myograph system in vitro. Blood pressure of carotid artery in rabbits was measured by using physiological data acquisition and analysis system in vivo. Results: Copper dose-dependently blunted NA-induced vasoconstriction of rat mesenteric artery. Copper-induced vasorelaxation was inhibited when the vessels were pretreated with NG-nitro-L-arginine methyl ester (L-NAME. Copper did not blunt high K+-induced vasoconstriction. Copper preincubation inhibited NA-evoked vasoconstriction and the inhibition was not affected by the presence of L-NAME. Copper preincubation showed no effect on high K+-evoked vasoconstriction. Copper chelator diethyldithiocarbamate trihydrate (DTC antagonized the vasoactivity induced by copper in rat mesenteric artery. In vivo experiments showed that copper injection (iv significantly decreased blood pressure of rabbits and NA or DTC injection (iv did not rescue the copper-induced hypotension and animal death. Conclusion: Copper blunted NA but not high K+-induced vasoconstriction of rat mesenteric artery. The acute effect of copper on NA-induced vasoconstriction was depended on nitric oxide (NO, but the effect of copper pretreatment on NA-induced vasoconstriction was independed on NO, suggesting that copper affected NA-induced vasoconstriction by two distinct mechanisms.

  18. Antagonism of the thromboxane-prostanoid receptor is cardioprotective against right ventricular pressure overload.

    Science.gov (United States)

    West, James D; Voss, Bryan M; Pavliv, Leo; de Caestecker, Mark; Hemnes, Anna R; Carrier, Erica J

    2016-06-01

    Right ventricular (RV) failure is the primary cause of death in pulmonary arterial hypertension (PAH) and is a significant cause of morbidity and mortality in other forms of pulmonary hypertension. There are no approved therapies directed at preserving RV function. F-series and E-series isoprostanes are increased in heart failure and PAH, correlate to the severity of disease, and can signal through the thromboxane-prostanoid (TP) receptor, with effects from vasoconstriction to fibrosis. The goal of these studies was to determine whether blockade of the TP receptor with the antagonist CPI211 was beneficial therapeutically in PAH-induced RV dysfunction. Mice with RV dysfunction due to pressure overload by pulmonary artery banding (PAB) were given vehicle or CPI211. Two weeks after PAB, CPI211-treated mice were protected from fibrosis with pressure overload. Gene expression arrays and immunoblotting, quantitative histology and morphometry, and flow cytometric analysis were used to determine the mechanism of CPI211 protection. TP receptor inhibition caused a near normalization of fibrotic area, prevented cellular hypertrophy while allowing increased RV mass, increased expression of antifibrotic thrombospondin-4, and blocked induction of the profibrotic transforming growth factor β (TGF-β) pathway. A thromboxane synthase inhibitor or low-dose aspirin failed to replicate these results, which suggests that a ligand other than thromboxane mediates fibrosis through the TP receptor after pressure overload. This study suggests that TP receptor antagonism may improve RV adaptation in situations of pressure overload by decreasing fibrosis and TGF-β signaling. PMID:27252848

  19. Exploring the structural basis for selenium/mercury antagonism in Allium fistulosum

    Energy Technology Data Exchange (ETDEWEB)

    McNear, Jr., David H.; Afton, Scott E.; Caruso, Joseph A. (UCIN); (Kentucky)

    2012-12-10

    While continuing efforts are devoted to studying the mutually protective effect of mercury and selenium in mammals, few studies have investigated the mercury-selenium antagonism in plants. In this study, we report the metabolic fate of mercury and selenium in Allium fistulosum (green onion) after supplementation with sodium selenite and mercuric chloride. Analysis of homogenized root extracts via capillary reversed phase chromatography coupled with inductively coupled plasma mass spectrometry (capRPLC-ICP-MS) suggests the formation of a mercury-selenium containing compound. Micro-focused synchrotron X-ray fluorescence mapping of freshly excised roots show Hg sequestered on the root surface and outlining individual root cells, while Se is more evenly distributed throughout the root. There are also discrete Hg-only, Se-only regions and an overall strong correlation between Hg and Se throughout the root. Analysis of the X-ray absorption near edge structure (XANES) spectra show a 'background' of methylselenocysteine within the root with discrete spots of SeO{sub 3}{sup 2-}, Se{sup 0} and solid HgSe on the root surface. Mercury outlining individual root cells is possibly binding to sulfhydryl groups or plasma membrane or cell wall proteins, and in some places reacting with reduced selenium in the rhizosphere to form a mercury(II) selenide species. Together with the formation of the root-bound mercury(II) selenide species, we also report on the formation of cinnabar (HgS) and Hg{sup 0} in the rhizosphere. The results presented herein shed light on the intricate chemical and biological processes occurring within the rhizosphere that influence Hg and Se bioavailability and will be instrumental in predicting the fate and assisting in the remediation of these metals in the environment and informing whether or not fruit and vegetable food selection from aerial plant compartments or roots from plants grown in Hg contaminated soils, are safe for consumption.

  20. Differential effects of prednisone and growth hormone on fuel metabolism and insulin antagonism in humans

    Energy Technology Data Exchange (ETDEWEB)

    Horber, F.F.; Marsh, H.M.; Haymond, M.W. (Mayo Clinic, Rochester, MN (USA))

    1991-01-01

    Human growth hormone (hGH) and prednisone cause insulin resistance and glucose intolerance. However, it is unknown whether hGH and prednisone antagonize insulin action on protein, fat, and carbohydrate metabolism by a common or independent mechanism. Therefore, protein, fat, and carbohydrate metabolism was assessed simultaneously in four groups of eight subjects each after 7 days of placebo, recombinant DNA hGH (rhGH; 0.1 mg.kg-1.day-1), prednisone (0.8 mg.kg-1.day-1), or rhGH and prednisone administration after an 18-h fast and during gut infusion of glucose and amino acids (fed state). Fasting plasma glucose concentrations were similar during placebo and rhGH but elevated (P less than 0.001) during combined treatment, whereas plasma insulin concentrations were higher (237 +/- 57 pmol/ml, P less than 0.001) during combined than during placebo, rhGH, or prednisone treatment (34, 52, and 91 pM, respectively). In the fed state, plasma glucose concentrations were elevated only during combined treatment (11.3 +/- 2.1 mM, P less than 0.001). Plasma insulin concentrations were elevated during therapy with prednisone alone and rhGH alone (667 +/- 72 and 564 +/- 65 pmol/ml, respectively, P less than 0.001) compared with placebo (226 +/- 44 pmol/ml) but lower than with the combined rhGH and prednisone treatment (1249 +/- 54 pmol/ml, P less than 0.01). Protein oxidation {sup 14}C leucine increased (P less than 0.001) with prednisone therapy, decreased (P less than 0.001) with rhGH treatment, and was normal during the combined treatment.

  1. Cerebral, spinal and peripheral inhibition of gastrointestinal transit by PI017: differential antagonism by naloxonazine

    Energy Technology Data Exchange (ETDEWEB)

    Williams, C.L.; Heyman, J.S.; Porreca, F.; Burks, T.F.

    1986-03-05

    The authors were interested in characterizing the relative importance of central (cerebral, spinal) and peripheral opioid receptors in inhibition of gastrointestinal transit. The mu-receptor selective agonist, (NMePhe/sup 3/,D-Pro/sup 4/)morphiceptin (PL017), was evaluated for its effectiveness in slowing gastrointestinal transit after subcutaneous, intracerebroventricular (i.c.v.) or intrathecal (i.th.) administration when given alone or after pretreatment with naloxonazine, an irreversible mu/sub 1/ selective opioid receptor antagonist. Male, ICR mice (20-25 g) were pretreated with saline, naloxone or naloxonazine (35 mg/kg, s.c.) 25 hr prior to testing. Gastrointestinal transit was evaluated in previously fasted (18 hr) mice by oral administration of a liquid radiolabelled marker (Na/sub 2//sup 51/CrO/sub 4/). I.th. PL017 (100-1000 ng) was effective in slowing transit, but was essentially insensitive to naloxone or naloxonazine pretreatment. PL017 produced a dose-related inhibition of transit when given by either the i.c.v. (100-1000 ng) or s.c.(1-10 mg/kg) route; this effect was not sensitive to naloxone pretreatment but was antagonized by naloxonazine. These results indicate that the opioid receptors mediating gastrointestinal transit in the brain and periphery may be mu/sub 1/. In contrast, the insensitivity to naloxonazine suggests that the gastrointestinal effects of PL017 in the spinal cord may be the result of activation of mu/sub 2/ or possibly delta opioid receptors.

  2. Interleukin-6 gene knockout antagonizes high-fat-induced trabecular bone loss.

    Science.gov (United States)

    Wang, Chunyu; Tian, Li; Zhang, Kun; Chen, Yaxi; Chen, Xiang; Xie, Ying; Zhao, Qian; Yu, Xijie

    2016-10-01

    The purpose of the study was to determine the roles of interleukin-6 (IL6) in fat and bone communication. Male wild-type (WT) mice and IL6 knockout (IL6(-/-)) mice were fed with either regular diet (RD) or high-fat diet (HFD) for 12 weeks. Bone mass and bone microstructure were evaluated by micro-computed tomography. Gene expression related to lipid and bone metabolisms was assayed with real-time quantitative polymerase chain reaction. Bone marrow cells from both genotypes were induced to differentiate into osteoblasts or osteoclasts, and treated with palmitic acid (PA). HFD increased the body weight and fat pad weight, and impaired lipid metabolism in both WT and IL6(-/-) mice. The dysregulation of lipid metabolism was more serious in IL6(-/-) mice. Trabecular bone volume fraction, trabecular bone number and trabecular bone thickness were significantly downregulated in WT mice after HFD than those in the RD (P < 0.05). However, these bone microstructural parameters were increased by 53%, 34% and 40%, respectively, in IL6(-/-) mice than those in WT mice on the HFD (P < 0.05). IL6(-/-) osteoblasts displayed higher alkaline phosphatase (ALP) activity and higher mRNA levels of Runx2 and Colla1 than those in WT osteoblasts both in the control and PA treatment group (P < 0.05). IL6(-/-) mice showed significantly lower mRNA levels of PPARγ and leptin and higher mRNA levels of adiponectin in comparison with WT mice on HFD. In conclusion, these findings suggested that IL6 gene deficiency antagonized HFD-induced bone loss. IL6 might bridge lipid and bone metabolisms and could be a new potential therapeutic target for lipid metabolism disturbance-related bone loss. PMID:27493246

  3. Breaking an Epigenetic Chromatin Switch: Curious Features of Hysteresis in Saccharomyces cerevisiae Telomeric Silencing

    Science.gov (United States)

    Nagaraj, Vijayalakshmi H.; Mukhopadhyay, Swagatam; Dayarian, Adel; Sengupta, Anirvan M.

    2014-01-01

    In addition to gene network switches, local epigenetic modifications to DNA and histones play an important role in all-or-none cellular decision-making. Here, we study the dynamical design of a well-characterized epigenetic chromatin switch: the yeast SIR system, in order to understand the origin of the stability of epigenetic states. We study hysteresis in this system by perturbing it with a histone deacetylase inhibitor. We find that SIR silencing has many characteristics of a non-linear bistable system, as observed in conventional genetic switches, which are based on activities of a few promoters affecting each other through the abundance of their gene products. Quite remarkably, our experiments in yeast telomeric silencing show a very distinctive pattern when it comes to the transition from bistability to monostability. In particular, the loss of the stable silenced state, upon increasing the inhibitor concentration, does not seem to show the expected saddle node behavior, instead looking like a supercritical pitchfork bifurcation. In other words, the ‘off’ state merges with the ‘on’ state at a threshold concentration leading to a single state, as opposed to the two states remaining distinct up to the threshold and exhibiting a discontinuous jump from the ‘off’ to the ‘on’ state. We argue that this is an inevitable consequence of silenced and active regions coexisting with dynamic domain boundaries. The experimental observations in our study therefore have broad implications for the understanding of chromatin silencing in yeast and beyond. PMID:25536038

  4. Breaking an epigenetic chromatin switch: curious features of hysteresis in Saccharomyces cerevisiae telomeric silencing.

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi H Nagaraj

    Full Text Available In addition to gene network switches, local epigenetic modifications to DNA and histones play an important role in all-or-none cellular decision-making. Here, we study the dynamical design of a well-characterized epigenetic chromatin switch: the yeast SIR system, in order to understand the origin of the stability of epigenetic states. We study hysteresis in this system by perturbing it with a histone deacetylase inhibitor. We find that SIR silencing has many characteristics of a non-linear bistable system, as observed in conventional genetic switches, which are based on activities of a few promoters affecting each other through the abundance of their gene products. Quite remarkably, our experiments in yeast telomeric silencing show a very distinctive pattern when it comes to the transition from bistability to monostability. In particular, the loss of the stable silenced state, upon increasing the inhibitor concentration, does not seem to show the expected saddle node behavior, instead looking like a supercritical pitchfork bifurcation. In other words, the 'off' state merges with the 'on' state at a threshold concentration leading to a single state, as opposed to the two states remaining distinct up to the threshold and exhibiting a discontinuous jump from the 'off' to the 'on' state. We argue that this is an inevitable consequence of silenced and active regions coexisting with dynamic domain boundaries. The experimental observations in our study therefore have broad implications for the understanding of chromatin silencing in yeast and beyond.

  5. Tomato Fruit Development and Ripening Are Altered by the Silencing of LeEIN2 Gene

    Institute of Scientific and Technical Information of China (English)

    Hong-Liang Zhu; Ben-Zhong Zhu; Yi Shao; Xiao-Guang Wang; Xi-Jin Lin; Yuan-Hong Xie; Ying-Cong Li; Hong-Yan Gao; Yun-Bo Luo

    2006-01-01

    Loss-of-function ethylene insensitive 2 (EIN2) mutations showed ethylene insensitivity in Arabidopsis,which indicated an essential role of EIN2 in ethylene signaling. However, the function of EIN2 in fruit ripening has not been investigated. To gain a better understanding of EIN2, the temporal regulation of LeEIN2 expression during tomato fruit development was analyzed. The expression of LeEIN2 was constant at different stages of fruit development, and was not regulated by ethylene. Moreover, LeEIN2-silenced tomato fruits were developed using a virus-induced gene silencing fruit system to study the role of LeEIN2 in tomato fruit ripening. Silenced fruits had a delay in fruit development and ripening, related to greatly descended expression of ethylene-related and ripening-related genes in comparison with those of control fruits. These results suggested LeEIN2 positively mediated ethylene signals during tomato development. In addition,there were fewer seeds and Iocules in the silenced fruit than those in the control fruit, like the phenotype of parthenocarpic tomato fruit. The content of auxin and the expression of auxin-regulated gene were declined in silenced fruit, which indicated that EIN2 might be important for crosstalk between ethylene and auxin hormones.

  6. A highly specific microRNA-mediated mechanism silences LTR retrotransposons of strawberry.

    Science.gov (United States)

    Šurbanovski, Nada; Brilli, Matteo; Moser, Mirko; Si-Ammour, Azeddine

    2016-01-01

    Small RNAs are involved in a plethora of functions in plant genomes. In general, transcriptional gene silencing is mediated by 24-nucleotide siRNAs and is required for maintaining transposable elements in a silenced state. However, microRNAs are not commonly associated with transposon silencing. In this study, we performed small RNA transcriptome and degradome analyses of the Rosaceae model plant Fragaria vesca (the woodland strawberry) at the genome-wide level, and identified miRNA families and their targets. We report a highly specific mechanism of LTR retrotransposon silencing mediated by an abundant, ubiquitously expressed miRNA (fve-miR1511) generated from a single locus. This miRNA specifically targets LTR retroelements, silencing them post-transcriptionally by perfectly pairing to the highly conserved primer binding site for methionyl initiator tRNA that is essential for reverse transcription. We investigated the possible origins of this miRNA, and present evidence that the pre-miR1511 hairpin structure probably derived from a locus coding for tRNA(iM) (et) through a single microinversion event. Our study shows that this miRNA targets retrotransposons specifically and constitutively, and contributes to features such as genome stability, size and architecture in a far more direct way than previously thought. PMID:26611654

  7. Functional analysis of gene-silencing suppressors from tomato yellow leaf curl disease viruses.

    Science.gov (United States)

    Luna, Ana P; Morilla, Gabriel; Voinnet, Olivier; Bejarano, Eduardo R

    2012-10-01

    Tomato yellow leaf curl disease (TYLCD) is caused by a complex of phylogenetically related Begomovirus spp. that produce similar symptoms when they infect tomato plants but have different host ranges. In this work, we have evaluated the gene-silencing-suppression activity of C2, C4, and V2 viral proteins isolated from the four main TYLCD-causing strains in Spain in Nicotiana benthamiana. We observed varying degrees of local silencing suppression for each viral protein tested, with V2 proteins from all four viruses exhibiting the strongest suppression activity. None of the suppressors were able to avoid the spread of the systemic silencing, although most produced a delay. In order to test the silencing-suppression activity of Tomato yellow leaf curl virus (TYLCV) and Tomato yellow leaf curl Sardinia virus (TYLCSV) proteins in a shared (tomato) and nonshared (bean) host, we established novel patch assays. Using these tools, we found that viral proteins from TYLCV were able to suppress silencing in both hosts, whereas TYLCSV proteins were only effective in tomato. This is the first time that viral suppressors from a complex of disease-causing geminiviruses have been subject to a comprehensive analysis using two economically important crop hosts, as well as the established N. benthamiana plant model. PMID:22712505

  8. The Malignant Phenotype of Breast Cancer Cells Is Reduced by COX-2 Silencing

    Directory of Open Access Journals (Sweden)

    Ioannis Stasinopoulos

    2008-11-01

    Full Text Available The cyclooxygenase (COX pathway is currently targeted for therapeutic intervention in different cancers. We have previously shown that silencing of COX-2 in the poorly differentiated metastatic breast cell line MDA-MB-231 by RNA interference markedly delayed tumor onset and inhibited metastasis. To understand the functional effects of COX-2 silencing underlying the inhibition of tumor growth and metastasis previously reported, we investigated changes in these cells for a number of cancer-associated phenotypes. Cyclooxygenase-2-silenced cells were less able to acidify tissue culture medium, a response that could partly be attributed to decreased lactate production or export detected by reduced lactate in the medium. Consistent with the significantly reduced transcript levels of hyaluronan synthase 2, an enzyme responsible for the total level of hyaluronan secreted by these cells, COX-2 silencing resulted in lower hyaluronan levels secreted in culture medium. Inhibition of human umbilical vein endothelial cell network association in a coculture assay was also observed in COX-2-silenced cells. These data highlight the functional role of COX-2 in pathways that mediate increased malignancy.

  9. Potential of Metal Fibre Felts as Passive Absorbers in Absorption Silencers

    Directory of Open Access Journals (Sweden)

    Björn Hinze

    2013-03-01

    Full Text Available The growing noise exposure of residents, due to a rising number of flights, causes significant impacts on physical health. Therefore it is necessary to reduce the noise emission of aircrafts. During take-off, the noise generated by the jet engines is dominating. One way to lower the noise emission of jet engines is to build an absorption silencer by using porous liners. Because of the high thermic and corrosive attacks as well as high fatigue loads, conventional absorbers cannot be used. A promising material is sintered metal fibre felts. This study investigates the suitability of metal fibre felts for the use as absorption material in silencers. The influences of pore morphology, absorption coefficient, determined with perpendicular sound incidence, as well as geometric parameters of the silencer to the damping are identified. To characterise the material, the parameters fibre diameter, porosity and thickness are determined using three-dimensional computer tomography images. The damping potential of absorption silencers is measured using an impedance tube, which was modified for transmission measurements. The essential parameter to describe the acoustic characteristics of porous materials is the flow resistivity. It depends on the size, shape and number of open pores in the material. Finally a connection between pore morphology, flow resistivity of the metal fibre felts and damping potential of the absorption silencer is given.

  10. Silence acts as politeness strategy in the classroom——A case study of Chinese teacher students in intercultural MA classroom

    Institute of Scientific and Technical Information of China (English)

    Zhong Yanghui

    2010-01-01

    @@ Introduction With the development of paralinguistics, nonverbal interactions have drawn more and more attention (Larry et.al 2000) and silence is considered as the nonverbal interaction strategy in communication activities. Linguists have explored silence from different perspectives. According to Saville and Tannen, silence is used to perform positive, negative and off-record politeness strate-gies(Saville, 1985; Tannen, 1985). Moreover, Kurzon identifies intentional and unintentional silence, referring the former as silence used intentionally as a strategy while the later is silence caused due to extreme anxiety, embarrass-ment or panic(Kurzon, 1998).

  11. BEX1 promotes imatinib-induced apoptosis by binding to and antagonizing BCL-2.

    Directory of Open Access Journals (Sweden)

    Qian Xiao

    Full Text Available An enhanced anti-apoptotic capacity of tumor cells plays an important role in the process of breakpoint cluster region/Abelson tyrosine kinase gene (BCR/ABL-independent imatinib resistance. We have previously demonstrated that brain expressed X-linked 1 (BEX1 was silenced in secondary imatinib-resistant K562 cells and that re-expression of BEX1 can restore imatinib sensitivity resulting in the induction of apoptosis. However, the mechanism by which BEX1 executes its pro-apoptotic function remains unknown. We identified B-cell lymphoma 2 (BCL-2 as a BEX1-interacting protein using a yeast two-hybrid screen. The interaction between BEX1 and BCL-2 was subsequently confirmed by co-immunoprecipitation assays. Like BCL-2, BEX1 was localized to the mitochondria. The region between 33K and 64Q on BEX1 is important for its localization to the mitochondria and its ability to interact with BCL-2. Additionally, we found that this region is essential for BEX1-regulated imatinib-induced apoptosis. Furthermore, we demonstrated that the interaction between BCL-2 and BEX1 promotes imatinib-induced apoptosis by suppressing the formation of anti-apoptotic BCL-2/BCL-2-associated X protein (BAX heterodimers. Our results revealed an interaction between BEX1 and BCL-2 and a novel mechanism of imatinib resistance mediated by the BEX1/BCL-2 pathway.

  12. Alpha fetoprotein antagonizes apoptosis induced by paclitaxel in hepatoma cells in vitro.

    Science.gov (United States)

    Zhu, Mingyue; Li, Wei; Lu, Yan; Dong, Xu; Chen, Yi; Lin, Bo; Xie, Xieju; Guo, Junli; Li, Mengsen

    2016-01-01

    Hepatocellular carcinoma (HCC) cell resistance to the effects of paclitaxel has not been adequately addressed. In this study, we found that paclitaxel significantly inhibited the viability of HLE, Bel 7402 and L-02 cells in a dose- and time-dependent manner. HLE cells and L-02 cells resisted the cytotoxicity of paclitaxel when transfected with pcDNA3.1-afp vectors. However, Bel 7402 cell sensitivity to paclitaxel was increased when transfected with alpha fetoprotein (AFP)-siRNA. Bel 7402 cell resistance to paclitaxel was associated with the expression of the "stemness" markers CD44 and CD133. Paclitaxel significantly inhibited growth and promoted apoptosis in HLE cells and L-02 cells by inducing fragmentation of caspase-3 and inhibiting the expression of Ras and Survivin, but pcDNA3.1-afp vectors prevented these effects. However, paclitaxel could not significantly promote the cleavage of caspase-3 or suppress the expression of Ras and Survivin in Bel 7402 cells. Silenced expression of AFP may be synergistic with paclitaxel to restrain proliferation and induce apoptosis, enhance cleavage of caspase-3, and suppress the expression of Ras and Survivin. Taken together, AFP may be an important molecule acting against paclitaxel-inhibited proliferation and induced apoptosis in HCC cells via repressing the activity of caspase-3 and stimulating the expression of Ras and Survivin. Targeted inhibition of AFP expression after treatment with paclitaxel is an available strategy for the therapy of patients with HCC. PMID:27255186

  13. Something Blossoms in Between: Silence-Phenomena as a Bordering Notions in Psychology.

    Science.gov (United States)

    Lehmann Oliveros, Olga V

    2016-03-01

    Mysterious yet unavoidable, silence-phenomena appear to us in inherent ambiguity. In its plurality of meanings, phenomena related to silence are often perceived as overwhelming because they transcend the communicative capacity of language making it a challenge for cultural psychology to understand its involvement in our processes of making sense of experience and existence. Human growth and development involve processes where presence, void and content, voice, sound and noise, motion, transition and stillness, have dialectic interactions. In this article I discuss silence-phenomena as a bordering notion in terms of its discursive quality, the silent quality of speech, and the awareness of the ineffable. In addition, I highlight the possible implications of such notion in the understanding of affect from the perspective of Semiotic Cultural Psychology. I also emphasize the importance of considering psychological borders as multi-dimensional, taking the phenomenological experience of temporality as an illustration, which is also related to high emotional involvement of attention. PMID:26232279

  14. The role of GW182 proteins in miRNA-mediated gene silencing.

    Science.gov (United States)

    Braun, Joerg E; Huntzinger, Eric; Izaurralde, Elisa

    2013-01-01

    GW182 family proteins are essential for microRNA-mediated gene silencing in animal cells. They are recruited to miRNA targets through direct interactions with Argonaute proteins and promote target silencing. They do so by repressing translation and enhancing mRNA turnover. Although the precise mechanism of action of GW182 proteins is not fully understood, these proteins have been shown to interact with the cytoplasmic poly(A)-binding protein (PABP) and with the PAN2-PAN3 and CCR4-NOT deadenylase complexes. These findings suggest that GW182 proteins function as scaffold proteins for the assembly of the multiprotein complex that silences miRNA targets. PMID:23224969

  15. Excavating silences and tensions of agency|passivity in science education reform

    Science.gov (United States)

    Rivera Maulucci, Maria S.

    2010-12-01

    I reflect on studies by Rodriguez and Carlone, Haun-Frank, and Kimmel to emphasize the ways in which they excavate silences in the science education literature related to linguistic and cultural diversity and situating the problem of reform in teachers rather than contextual factors, such as traditional schooling discourses and forces that serve to marginalize science. I propose that the current push for top-down reform and accountability diminishes opportunities for receptivity, learning with and from students in order to transform teachers' practices and promote equity in science education. I discuss tensions of agency and passivity in science education reform and argue that attention to authentic caring constitutes another silence in the science education literature. I conclude that the current policy context positions teachers and science education researchers as tempered radicals struggling against opp(reg)ressive reforms and that there is a need for more studies to excavate these and other silences.

  16. Study of the dispersion of natural gas issuing from compressor stations through silencers with upper cover.

    Science.gov (United States)

    García, J; Migoya, E; Lana, J A; Crespo, A

    2008-04-15

    The aim of the present study is the simulation of the dispersion of natural gas issuing from the silencer of compressor stations during vent operations. The objective is to analyze the dispersion of the gas emitted under different conditions of mass flow rate at the exit and ambient cross-flow velocity. We have considered a silencer with an upper cover to protect it from the rain and the fall of objects. The influence of the upper cover of the silencer on the dispersion of natural gas has also been studied, and non-dimensional approaches of the model have been proposed to simplify the problem. Seven different cases have been solved, using two models: a 3D model based on the commercial code FLUENT, and a simplified quasi-one-dimensional model. The results obtained in both cases have been compared, and the range of validity of the one-dimensional model in non-dimensional form has been discussed. PMID:17875364

  17. Gene silencing by RNA interference in the house dust mite, Dermatophagoides pteronyssinus.

    Science.gov (United States)

    Marr, Edward J; Sargison, Neil D; Nisbet, Alasdair J; Burgess, Stewart T G

    2015-12-01

    This is the first report of gene silencing by RNA interference (RNAi) in the European house dust mite, Dermatophagoides pteronyssinus, Trouessart, 1897. Using a non-invasive immersion method first developed for the honey bee mite, Varroa destructor, a significant reduction in the expression of D. pteronyssinus glutathione-S-transferase mu-class 1 enzyme (DpGST-mu1) was achieved following overnight immersion in double stranded RNA encoding DpGST-mu1. Although no detrimental phenotypic changes were observed following silencing, this technique can now be used to address fundamental physiological questions and assess the potential therapeutic benefit in silencing D. pteronyssinus target genes in selected domestic situations of high human-mite interface. PMID:26212476

  18. Global Effects on Gene Expression in Fission Yeast by Silencing and RNA Interference Machineries

    DEFF Research Database (Denmark)

    Hansen, Klavs R.; Burns, G.; Mata, J.; Volpe, T. A.; Martienssen, R. A.; Bähler, J.; Thon, Genevieve

    2005-01-01

    Histone modifications influence gene expression in complex ways. The RNA interference (RNAi) machinery can repress transcription by recruiting histone-modifying enzymes to chromatin, although it is not clear whether this is a general mechanism for gene silencing or whether it requires repeated...... genes were repressed by both the silencing and RNAi machineries, with transcripts from centromeric repeats and Tf2 retrotransposons being notable exceptions. We found no correlation between repression by RNAi and proximity to LTRs, and the wtf family of repeated sequences seems to be repressed by...... histone deacetylation independent of RNAi. Our data indicate that the RNAi and Clr proteins show only a limited functional overlap and that the Clr proteins play more global roles in gene silencing....

  19. Silencing of VAMP3 inhibits cell migration and integrin-mediated adhesion

    International Nuclear Information System (INIS)

    Integrins are transmembrane receptors for cell adhesion to the extracellular matrix. In cell migration, integrins are endocytosed from the plasma membrane or the cell surface, transported in vesicles and exocytosed actively at the cell front. In the present study, we examined the roles of VAMP3, a SNARE protein that mediates exocytosis, in cell migration and integrin trafficking. Small interfering RNA (siRNA)-induced silencing of VAMP3 inhibited chemotactic cell migration by more than 60% without affecting cell proliferation. VAMP3 silencing reduced the levels of β1 integrin at the cell surface but had no effect on total cellular β1 integrin, indicating that VAMP3 is required for trafficking of β1 integrin to the plasma membrane. Furthermore, VAMP3 silencing diminished cell adhesion to laminin but not to fibronectin or collagen. Taken together, these data suggest that VAMP3-dependent integrin trafficking is crucial in cell migration and cell adhesion to laminin.

  20. MAGNUM OPUS: CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS BIOLOGY AND PROKARYOTIC GENE SILENCING

    Directory of Open Access Journals (Sweden)

    Prem Saran Tirumalai

    2013-01-01

    Full Text Available Gene Silencing was a technology that was established in eukaryotic system a decade ago and is being used as a research tool widely. However, prokaryotic gene silencing was not workable, till recently a team of researchers from the University of Georgia have proved it possible. Where they have shown that short motif sequences determines the targets of the prokaryotic Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR defence system is regulated by RNA guided Cas protein complex. Thus role of CRISPR system in microbial defense against foreign genetic material (Plasmid or Phages is an important milestone in the field of microbial molecular biology/biotechnology. These findings will make it easier to understand the significance of a gene, metabolically or physiologically. The revelation by this novel finding by core group of researcher is indeed, Mangum opus. This article is a commentary, to bring to light, prokaryotic gene silencing as one of the latest advances in prokaryotic science.

  1. Gene silencing and Polycomb group proteins: an overview of their structure, mechanisms and phylogenetics.

    Science.gov (United States)

    Golbabapour, Shahram; Majid, Nazia Abdul; Hassandarvish, Pouya; Hajrezaie, Maryam; Abdulla, Mahmood Ameen; Hadi, A Hamid A

    2013-06-01

    DNA methylation, histone modifications, and chromatin configuration are crucially important in the regulation of gene expression. Among these epigenetic mechanisms, silencing the expression of certain genes depending on developmental stage and tissue specificity is a key repressive system in genome programming. Polycomb (Pc) proteins play roles in gene silencing through different mechanisms. These proteins act in complexes and govern the histone methylation profiles of a large number of genes that regulate various cellular pathways. This review focuses on two main Pc complexes, Pc repressive complexes 1 and 2, and their phylogenetic relationship, structures, and function. The dynamic roles of these complexes in silencing will be discussed herein, with a focus on the recruitment of Pc complexes to target genes and the key factors involved in their recruitment. PMID:23692361

  2. Generation of tobacco lines with widely different reduction in nicotine levels via RNA silencing approaches

    Indian Academy of Sciences (India)

    Peng Wang; Zhifeng Liang; Jia Zeng Wenchao; Wenchao Li; Xiaofen Sun; Zhiqi Miao; Kexuan Tang

    2008-06-01

    Issues related to the nicotine content of tobacco have been public concerns. Several reports have described decreasing nicotine levels by silencing the putrescine N-methyltransferase (PMT) genes, but the reported variations of nicotine levels among transgenic lines are relatively low in general. Here we describe the generation in tobacco (Nicotiana tabacum) lines with widely different, reduced nicotine levels using three kinds of RNA-silencing approaches. The relative efficacies of suppression were compared among the three approaches regarding the aspect of nicotine level in tobacco leaves. By suppressing expression of the PMT genes, over 200 transgenic lines were obtained with nicotine levels reduced by 9.1–96.7%. RNA interference (RNAi) was the most efficient method of reducing the levels of nicotine, whereas cosuppression and antisense methods were less effective. This report gives clues to the efficient generation of plants with a variety of metabolite levels, and the results demonstrate the relative efficiencies of various RNA-silencing methods.

  3. From silencing the self to action: experiences of women living with HIV/AIDS.

    Science.gov (United States)

    DeMarco, R F; Miller, K H; Patsdaughter, C A; Chisholm, M; Grindel, C G

    1998-01-01

    Feminist literature has demonstrated that women often maintain behaviors that support silencing of their voices. The critical issue is whether the silencing experience is (a) a destructive process of burying feelings and needs, (b) a protective strategy to preserve personal and professional relationships which they value, (c) a coping mechanism to divorce themselves from an androcentric/ethnocentric health care culture, or all of these. The transition from silence to action may be a process of reacting to a threat to self (i.e., HIV/AIDS diagnosis) where gender normative behaviors become irrelevant and self-advocacy becomes paramount for survival. Alternatively, the transition may be a conscious process of gaining insight into past behaviors that have been learned and culturally supported and making purposeful changes. Data for this study were extracted for secondary analysis from data from a larger study on experiences and needs of persons living with HIV/AIDS. Data were obtained from transcripts from three focus groups (N = 14 women) and six individual interviews. Women ranged in age from 21 to 55; 9 were European American, 7 were African American, and 4 were Latina American. Data were content analyzed and organized using four categories proposed by Jack (1991): (a) externalized self-perception, (b) care as self-sacrifice, (c) silencing the self, and (d) the divided self. Data supported that women with HIV/AIDS reported all four categories of silencing behaviors, particularly early in the HIV trajectory. For some women, an HIV/AIDS diagnosis ignited them to speak for themselves and to shape their own lives based on feelings and needs. For others, peer or professional support or both was the catalyst for the transition from silence to action. Findings suggest interventions that would assist women in judging themselves by internal versus external standards, putting their own needs before the perceived needs of others, expressing themselves toward action rather than

  4. Silencing and Innate Immunity in Plant Defense Against Viral and Non-Viral Pathogens

    Directory of Open Access Journals (Sweden)

    Anna S. Zvereva

    2012-10-01

    Full Text Available The frontline of plant defense against non-viral pathogens such as bacteria, fungi and oomycetes is provided by transmembrane pattern recognition receptors that detect conserved pathogen-associated molecular patterns (PAMPs, leading to pattern-triggered immunity (PTI. To counteract this innate defense, pathogens deploy effector proteins with a primary function to suppress PTI. In specific cases, plants have evolved intracellular resistance (R proteins detecting isolate-specific pathogen effectors, leading to effector-triggered immunity (ETI, an amplified version of PTI, often associated with hypersensitive response (HR and programmed cell death (PCD. In the case of plant viruses, no conserved PAMP was identified so far and the primary plant defense is thought to be based mainly on RNA silencing, an evolutionary conserved, sequence-specific mechanism that regulates gene expression and chromatin states and represses invasive nucleic acids such as transposons. Endogenous silencing pathways generate 21-24 nt small (sRNAs, miRNAs and short interfering (siRNAs, that repress genes post-transcriptionally and/or transcriptionally. Four distinct Dicer-like (DCL proteins, which normally produce endogenous miRNAs and siRNAs, all contribute to the biogenesis of viral siRNAs in infected plants. Growing evidence indicates that RNA silencing also contributes to plant defense against non-viral pathogens. Conversely, PTI-based innate responses may contribute to antiviral defense. Intracellular R proteins of the same NB-LRR family are able to recognize both non-viral effectors and avirulence (Avr proteins of RNA viruses, and, as a result, trigger HR and PCD in virus-resistant hosts. In some cases, viral Avr proteins also function as silencing suppressors. We hypothesize that RNA silencing and innate immunity (PTI and ETI function in concert to fight plant viruses. Viruses counteract this dual defense by effectors that suppress both PTI-/ETI-based innate responses

  5. (Regendering Memories of the Kosovo Liberation army: The Silenced Guerrilla of Women

    Directory of Open Access Journals (Sweden)

    Virginia Stephens

    2014-03-01

    Full Text Available Across the world and throughout history, women have played an active part in combat (Enloe, 1989; and Enloe, 2000 and yet discourses of war tend to be male domi-nated. Is the forgotten warfare of women in combat due to the absence of social exchanges or a deliberate choice of silencing? This paper argues for the latter by investi-gating the silencing of female combatants using the ex-ample of the Kosovo Liberation Army (KLA, and their subsequent lack of visibility and input in Kosovo’s na-tion-building project [1]. Based on preliminary findings from an oral history project with female KLA combat-ants, this paper seeks to question why, after having oc-cupied such a key place in combat, women have not de-fended their history, their words, their experiences – their memories – of their time at the front. It then ex-plores the different forces behind the silencing of their roles as combatants and the types of narrative allowed in collective memory and remembering. Breaking the silence of women combatants encourages an engage-ment with various gender frameworks that are absent from nation building narratives, and an understanding of what women are cultural products of. This paper does not aim to find heroes or glorify the hegemonic war narratives of the KLA, but rather to draw particular attention to the role of women combatants in post-war nation-building projects, such as Kosovo, and the silenc-ing of that role. In doing so, such a project intends to reframe how we remember and write national histories, as well as helping to shed light on the cultural construc-tion of gendered identities in a post-war era.

  6. Specific degradation of 3[prime prime or minute] regions of GUS mRNA in posttranscriptionally silenced tobacco lines may be related to 5[prime prime or minute]-3[prime prime or minute] spreading of silencing

    DEFF Research Database (Denmark)

    Braunstein, T.H.; Moury, B.; Johannessen, M.M.;

    2002-01-01

    genetic background are not major determinants of silencing target regions. We also show that virus-induced gene silencing (VIGS) of GUS in Nicotiana benthamiana is induced equally effectively with Potato virus X carrying either the 5' or 3' third of the GUS coding region. This indicates that both regions...

  7. Design of a PROTAC that antagonizes and destroys the cancer-forming X-protein of the hepatitis B virus

    International Nuclear Information System (INIS)

    Highlights: • A novel proteolysis targeting chimeric molecule (PROTAC) to treat hepatitis B. • The PROTAC antagonizes and destroys the X-protein of the hepatitis B virus. • The PROTAC is a fusion of the X-protein oligomerization and instability domains. • The oligomerization domain is a dominant-negative inhibitor of X-protein function. • X-protein-targeting PROTACs have potential to prevent hepatocellular carcinoma. - Abstract: The X-protein of the hepatitis B virus (HBV) is essential for virus infection and contributes to the development of HBV-induced hepatocellular carcinoma (HCC), a disease which causes more than one million deaths each year. Here we describe the design of a novel PROTAC (proteolysis targeting chimeric molecule) capable of simultaneously inducing the degradation of the X-protein, and antagonizing its function. The PROTAC was constructed by fusing the N-terminal oligomerization and C-terminal instability domains of the X-protein to each other, and rendering them cell-permeable by the inclusion of a polyarginine cell-penetrating peptide (CPP). It was predicted that the oligomerization domain would bind the X-protein, and that the instability domain would cause the X-protein to be targeted for proteasomal degradation. Addition of the PROTAC to HepG2 liver cancer cells, engineered to express full-length and C-terminally truncated forms of the X-protein, resulted in the degradation of both forms of the X-protein. A cell-permeable stand-alone form of the oligomerization domain was taken up by HepG2 cells, and acted as a dominant-negative inhibitor, causing inhibition of X-protein-induced apoptosis. In summary, the PROTAC described here induces the degradation of the X-protein, and antagonizes its function, and warrants investigation in a preclinical study for its ability to prevent or treat HBV infection and/or the development of HCC

  8. NK4 antagonizes Tbx1/10 to promote cardiac versus pharyngeal muscle fate in the ascidian second heart field.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2013-12-01

    Full Text Available The heart and head muscles share common developmental origins and genetic underpinnings in vertebrates, including humans. Parts of the heart and cranio-facial musculature derive from common mesodermal progenitors that express NKX2-5, ISL1, and TBX1. This ontogenetic kinship is dramatically reflected in the DiGeorge/Cardio-Velo-Facial syndrome (DGS/CVFS, where mutations of TBX1 cause malformations in the pharyngeal apparatus and cardiac outflow tract. Cardiac progenitors of the first heart field (FHF do not require TBX1 and segregate precociously from common progenitors of the second heart field (SHF and pharyngeal muscles. However, the cellular and molecular mechanisms that govern heart versus pharyngeal muscle specification within this lineage remain elusive. Here, we harness the simplicity of the ascidian larva to show that, following asymmetric cell division of common progenitors, NK4/NKX2-5 promotes GATAa/GATA4/5/6 expression and cardiac specification in the second heart precursors by antagonizing Tbx1/10-mediated inhibition of GATAa and activation of Collier/Olf/EBF (COE, the determinant of atrial siphon muscle (ASM specification. Our results uncover essential regulatory connections between the conserved cardio-pharyngeal factor Tbx1/10 and muscle determinant COE, as well as a mutual antagonism between NK4 and Tbx1/10 activities upstream of GATAa and COE. The latter cross-antagonism underlies a fundamental heart versus pharyngeal muscle fate choice that occurs in a conserved lineage of cardio-pharyngeal progenitors. We propose that this basic ontogenetic motif underlies cardiac and pharyngeal muscle development and evolution in chordates.

  9. Design of a PROTAC that antagonizes and destroys the cancer-forming X-protein of the hepatitis B virus

    Energy Technology Data Exchange (ETDEWEB)

    Montrose, Kristopher; Krissansen, Geoffrey W., E-mail: gw.krissansen@auckland.ac.nz

    2014-10-31

    Highlights: • A novel proteolysis targeting chimeric molecule (PROTAC) to treat hepatitis B. • The PROTAC antagonizes and destroys the X-protein of the hepatitis B virus. • The PROTAC is a fusion of the X-protein oligomerization and instability domains. • The oligomerization domain is a dominant-negative inhibitor of X-protein function. • X-protein-targeting PROTACs have potential to prevent hepatocellular carcinoma. - Abstract: The X-protein of the hepatitis B virus (HBV) is essential for virus infection and contributes to the development of HBV-induced hepatocellular carcinoma (HCC), a disease which causes more than one million deaths each year. Here we describe the design of a novel PROTAC (proteolysis targeting chimeric molecule) capable of simultaneously inducing the degradation of the X-protein, and antagonizing its function. The PROTAC was constructed by fusing the N-terminal oligomerization and C-terminal instability domains of the X-protein to each other, and rendering them cell-permeable by the inclusion of a polyarginine cell-penetrating peptide (CPP). It was predicted that the oligomerization domain would bind the X-protein, and that the instability domain would cause the X-protein to be targeted for proteasomal degradation. Addition of the PROTAC to HepG2 liver cancer cells, engineered to express full-length and C-terminally truncated forms of the X-protein, resulted in the degradation of both forms of the X-protein. A cell-permeable stand-alone form of the oligomerization domain was taken up by HepG2 cells, and acted as a dominant-negative inhibitor, causing inhibition of X-protein-induced apoptosis. In summary, the PROTAC described here induces the degradation of the X-protein, and antagonizes its function, and warrants investigation in a preclinical study for its ability to prevent or treat HBV infection and/or the development of HCC.

  10. The Miranda Right to silence in criminal trial : an economic analysis

    OpenAIRE

    Lang, Günther

    2005-01-01

    This paper analyzes the strategic implications for criminal trial of the existence of the famous Miranda Right to Silence in U.S. law doctrine. The right confers to the defendant the privilege that, in the context of a signalling game, i. e. the trial, no adverse conclusions may be drawn from his exercise of the right. It is shown that Miranda reduces wrongful confessions and convictions, at the price, however, of setting free guilty defendants as well. The rate of silence is affected only wh...

  11. Learning to be silent: theological and philosophical reflections on silence and transcendence

    OpenAIRE

    Wardley, Kenneth Jason

    2010-01-01

    ‘Libère-moi de la trop longue parole.’ (Maurice Blanchot, Le pas au-delà, 1973) Michèle le Doeuff suggested that theology rests upon a prior silencing of philosophy; the work of Jean-Yves Lacoste is unconcerned with any strict distinction between the disciplines where theology is an unsystematic, fragmentary and, above all, ethical activity, reminiscent of Stoker’s account of Derrida and the fourth type of messianic transcendence. While suffering can reduce theology to silence thi...

  12. Autocidal control of ticks by silencing of a single gene by RNA interference

    International Nuclear Information System (INIS)

    Ticks impact human and animal health worldwide and new control methods are needed to circumvent draw-backs of tick control by acaricide application including selection of drug resistant ticks and environmental pollution. Using RNA interference we silenced the expression of a single gene, subolesin, and produced ticks with diminished reproductive performance and prevented successful mating and production of viable offspring. We propose a sterile acarine technique (SAT) for reduction of tick populations by release of subolesin-silenced ticks. Conservation of subolesin among tick species suggests that SAT may be useful for control of many medically and economically important tick species. (author)

  13. Simulation of RNA Silencing Pathway for Time-Dependent Transgene Transcription Rate

    Science.gov (United States)

    Yang, Xiao-Dong; Mahapatra, Debiprosad Roy; Melnik, Roderick V. N.

    2007-11-01

    The synthesis of dsRNA is analyzed using a pathway model with amplifications caused by the aberrant RNAs. The transgene influx rate is assumed time-decaying considering the fact that the number of transgenes can not be infinite. The dynamics of the transgene induced RNA silencing is investigated using a system of coupled nonautonomous ordinary nonlinear differential equations which describe the model phenomenologically. The silencing phenomena are detected after a period of transcription. Important contributions of certain parameters are discussed with several numerical examples.

  14. Mammalian hyperplastic discs homolog EDD regulates microRNA-mediated gene silencing

    OpenAIRE

    Su, Hong; Meng, Shuxia; Lu, Yanyan; Trombly, Melanie I.; Chen, Jian; Lin, Chengyi; Turk, Anita; Wang, Xiaozhong

    2011-01-01

    MicroRNAs (miRNAs) regulate gene expression through translation repression and mRNA destabilization. However, the molecular mechanisms of miRNA silencing are still not well defined. Using a genetic screen in mouse embryonic stem (ES) cells, we identify mammalian hyperplastic discs protein EDD, a known E3 ubiquitin ligase, as a key component of the miRNA silencing pathway. ES cells deficient for EDD are defective in miRNA function and exhibit growth defects. We demonstrate that E3 ubiquitin li...

  15. Redundancy of the Two Dicer Genes in Transgene-Induced Posttranscriptional Gene Silencing in Neurospora crassa†

    OpenAIRE

    Catalanotto, Caterina; Pallotta, Massimiliano; Refalo, Paul; Sachs, Matthew S.; Vayssie, Laurence; Macino, Giuseppe; Cogoni, Carlo

    2004-01-01

    RNA interference (RNAi) in animals, cosuppression in plants, and quelling in fungi are homology-dependent gene silencing mechanisms in which the introduction of either double-stranded RNA (dsRNA) or transgenes induces sequence-specific mRNA degradation. These phenomena share a common genetic and mechanistic basis. The accumulation of short interfering RNA (siRNA) molecules that guide sequence-specific mRNA degradation is a common feature in both silencing mechanisms, as is the component of th...

  16. High potency silencing by single-stranded boranophosphate siRNA

    OpenAIRE

    Hall, Allison H. S.; Wan, Jing; Spesock, April; Sergueeva, Zinaida; Shaw, Barbara Ramsay; Alexander, Kenneth A.

    2006-01-01

    In RNA interference (RNAi), double-stranded short interfering RNA (ds-siRNA) inhibits expression from complementary mRNAs. Recently, it was demonstrated that short, single-stranded antisense RNA (ss-siRNA) can also induce RNAi. While ss-siRNA may offer several advantages in both clinical and research applications, its overall poor activity compared with ds-siRNA has prevented its widespread use. In contrast to the poor gene silencing activity of native ss-siRNA, we found that the silencing ac...

  17. Viral Class 1 RNase III Involved in Suppression of RNA Silencing

    OpenAIRE

    Kreuze, Jan F.; Savenkov, Eugene I.; Cuellar, Wilmer; Li, Xiangdong; Valkonen, Jari P. T.

    2005-01-01

    Double-stranded RNA (dsRNA)-specific endonucleases belonging to RNase III classes 3 and 2 process dsRNA precursors to small interfering RNA (siRNA) or microRNA, respectively, thereby initiating and amplifying RNA silencing-based antiviral defense and gene regulation in eukaryotic cells. However, we now provide evidence that a class 1 RNase III is involved in suppression of RNA silencing. The single-stranded RNA genome of sweet potato chlorotic stunt virus (SPCSV) encodes an RNase III (RNase3)...

  18. A 22-nt artificial microRNA mediates widespread RNA silencing in Arabidopsis

    OpenAIRE

    McHale, Marcus; Eamens, Andrew L.; Finnegan, E Jean; Waterhouse, Peter M

    2013-01-01

    It is known that 22-nucleotide (nt) microRNAs (miRNAs) derived from asymmetric duplexes trigger phased small-interfering RNA (phasiRNA) production from complementary targets. Here we investigate the efficacy of 22-nt artificial miRNA (amiRNA)-mediated RNA silencing relative to conventional hairpin RNA (hpRNA) and 21-nt amiRNA-mediated RNA silencing. CHALCONE SYNTHASE (CHS) was selected as a target in Arabidopsis thaliana due to the obvious and non-lethal loss of anthocyanin accumulation upon ...

  19. RNA silencing in plants by the expression of siRNA duplexes

    OpenAIRE

    Lu, Shanfa; Shi, Rui; Tsao, Cheng-Chung; Yi, Xiaoping; Li, Laigeng; Chiang, Vincent L.

    2004-01-01

    In animal cells, stable RNA silencing can be achieved by vector-based small interfering RNA (siRNA) expression system, in which Pol III RNA gene promoters are used to drive the expression of short hairpin RNA, however, this has not been demonstrated in plants. Whether Pol III RNA gene promoter is capable of driving siRNA expression in plants is unknown. Here, we report that RNA silencing was achieved in plants through stable expression of short hairpin RNA, which was driven by Pol III RNA gen...

  20. Positive roles of SAS2 in DNA replication and transcriptional silencing in yeast

    OpenAIRE

    Zou, Yanfei; Bi, Xin

    2008-01-01

    Sas2p is a histone acetyltransferase implicated in the regulation of transcriptional silencing, and ORC is the six-subunit origin recognition complex involved in the initiation of DNA replication and the establishment of transcriptionally silent chromatin by silencers in yeast. We show here that SAS2 deletion (sas2Δ) exacerbates the temperature sensitivity of the ORC mutants orc2-1 and orc5-1. Moreover, sas2Δ and orc2-1 have a synthetic effect on cell cycle progression through S phase and ini...

  1. Simulation and Measurements of Small Arms Blast Wave Overpressure in the Process of Designing a Silencer

    Directory of Open Access Journals (Sweden)

    Hristov Nebojša

    2015-02-01

    Full Text Available Simulation and measurements of muzzle blast overpressure and its physical manifestations are studied in this paper. The use of a silencer can have a great influence on the overpressure intensity. A silencer is regarded as an acoustic transducer and a waveguide. Wave equations for an acoustic dotted source of directed effect are used for physical interpretation of overpressure as an acoustic phenomenon. Decomposition approach has proven to be suitable to describe the formation of the output wave of the wave transducer. Electroacoustic analogies are used for simulations. A measurement chain was used to compare the simulation results with the experimental ones.

  2. An interaction of ondansetron and dexamethasone antagonizing cisplatin-induced acute and delayed emesis in the ferret.

    OpenAIRE

    Rudd, J. A.; Naylor, R. J.

    1996-01-01

    1. Cisplatin, 5 mg kg-1, i.p., administered as a single treatment, induced an acute (day 1) and delayed (days 2 and 3) emetic response in the ferret that was used to investigate the potential anti-emetic activity of ondansetron and dexamethasone and their interaction over a three day period. 2. Ondansetron, 1 mg kg-1, i.p., administered three times per day in two experiments, antagonized significantly the retching and vomiting that occurred on days 1 and 2 by 60-76 and 73-84%. On the third da...

  3. Structural determinants in phycotoxins and AChBP conferring high affinity binding and nicotinic AChR antagonism

    OpenAIRE

    Bourne, Yves; Radić, Zoran; Aráoz, Rómulo; Talley, Todd T.; Benoit, Evelyne; Servent, Denis; Taylor, Palmer; Molgó, Jordi; Marchot, Pascale

    2010-01-01

    Spirolide and gymnodimine macrocyclic imine phycotoxins belong to an emerging class of chemical agents associated with marine algal blooms and shellfish toxicity. Analysis of 13-desmethyl spirolide C and gymnodimine A by binding and voltage-clamp recordings on muscle-type α12βγδ and neuronal α3β2 and α4β2 nicotinic acetylcholine receptors reveals subnanomolar affinities, potent antagonism, and limited subtype selectivity. Their binding to acetylcholine-binding proteins (AChBP), as soluble rec...

  4. Detection of Fusarium spp. and Trichoderma spp. and antagonism of Trichoderma sp. in soybean under no-tillage

    OpenAIRE

    Paola Mendes Milanesi; Elena Blume; Marlove Fátima Brião Muniz; Lia Rejane Silveira Reiniger; Zaida Inês Antoniolli; Emanuele Junges; Manoeli Lupatini

    2013-01-01

    This study aimed i) to quantify the occurrence of Fusarium spp. and Trichoderma spp. in rhizospheric soil, with and without symptoms of Sudden Death Syndrome (SDS) in eight soybean genotypes; ii) morphologically identify isolates of Fusarium spp. from roots with SDS; iii) evaluate the antagonism between Trichoderma spp. and Fusarium spp. isolates from rhizospheric soil and roots from with and without SDS, respectively; and iv) characterize through the ITS1-5.8S-ITS2 region of rDNA the isolate...

  5. SlmA Antagonism of FtsZ Assembly Employs a Two-pronged Mechanism like MinCD

    OpenAIRE

    Shishen Du; Joe Lutkenhaus

    2014-01-01

    Assembly of the Z-ring over unsegregated nucleoids is prevented by a process called nucleoid occlusion (NO), which in Escherichia coli is partially mediated by SlmA. SlmA is a Z ring antagonist that is spatially regulated and activated by binding to specific DNA sequences (SlmA binding sites, SBSs) more abundant in the origin proximal region of the chromosome. However, the mechanism by which SBS bound SlmA (activated form) antagonizes Z ring assembly is controversial. Here, we report the isol...

  6. Orexin-1 receptor blockade dysregulates REM sleep in the presence of orexin-2 receptor antagonism

    Directory of Open Access Journals (Sweden)

    Christine eDugovic

    2014-02-01

    Full Text Available In accordance with the prominent role of orexins in the maintenance of wakefulness via activation of orexin-1 (OX1R and orexin-2 (OX2R receptors, various dual OX1/2R antagonists have been shown to promote sleep in animals and humans. While selective blockade of OX2R seems to be sufficient to initiate and prolong sleep, the beneficial effect of additional inhibition of OX1R remains controversial. The relative contribution of OX1R and OX2R to the sleep effects induced by a dual OX1/2R antagonist was further investigated in the rat, and specifically on rapid eye movement (REM sleep since a deficiency of the orexin system is associated with narcolepsy/cataplexy based on clinical and pre-clinical data. As expected, the dual OX1/2R antagonist SB-649868 was effective in promoting non-REM (NREM and REM sleep following oral dosing (10 and 30 mg/kg at the onset of the dark phase. However, a disruption of REM sleep was evidenced by a more pronounced reduction in the onset of REM as compared to NREM sleep, a marked enhancement of the REM/total sleep ratio, and the occurrence of a few episodes of direct wake to REM sleep transitions (REM intrusion. When administered subcutaneously, the OX2R antagonist JNJ-10397049 (10 mg/kg increased NREM duration whereas the OX1R antagonist GSK-1059865 (10 mg/kg did not alter sleep. REM sleep was not affected either by OX2R or OX1R blockade alone, but administration of the OX1R antagonist in combination with the OX2R antagonist induced a significant reduction in REM sleep latency and an increase in REM sleep duration at the expense of the time spent in NREM sleep. These results indicate that additional blockade of OX1R to OX2R antagonism elicits a dysregulation of REM sleep by shifting the balance in favor of REM sleep at the expense of NREM sleep that may increase the risk of adverse events. Translation of this hypothesis remains to be tested in the clinic.

  7. Novel anti-HER2 monoclonal antibodies: synergy and antagonism with tumor necrosis factor-α

    International Nuclear Information System (INIS)

    anti-HER2 antibody inhibited Akt and ERK1/2 phosphorylation leading to cyclin D1 accumulation and growth arrest in SK-BR-3 cells, independently from TNF-α. Novel antibodies against extracellular domain of HER2 may serve as potent anti-cancer bioactive molecules. Cell-dependent synergy and antagonism between anti-HER2 antibodies and TNF-α provide evidence for a complex interplay between HER2 and TNF-α signaling pathways. Such complexity may drastically affect the outcome of HER2-directed therapeutic interventions

  8. Novel anti-HER2 monoclonal antibodies: synergy and antagonism with tumor necrosis factor-α

    Directory of Open Access Journals (Sweden)

    Ceran Ceyhan

    2012-10-01

    , but antagonistically on BT-474 cells. A representative anti-HER2 antibody inhibited Akt and ERK1/2 phosphorylation leading to cyclin D1 accumulation and growth arrest in SK-BR-3 cells, independently from TNF-α. Conclusions Novel antibodies against extracellular domain of HER2 may serve as potent anti-cancer bioactive molecules. Cell-dependent synergy and antagonism between anti-HER2 antibodies and TNF-α provide evidence for a complex interplay between HER2 and TNF-α signaling pathways. Such complexity may drastically affect the outcome of HER2-directed therapeutic interventions.

  9. Orexin-1 receptor blockade dysregulates REM sleep in the presence of orexin-2 receptor antagonism.

    Science.gov (United States)

    Dugovic, Christine; Shelton, Jonathan E; Yun, Sujin; Bonaventure, Pascal; Shireman, Brock T; Lovenberg, Timothy W

    2014-01-01

    In accordance with the prominent role of orexins in the maintenance of wakefulness via activation of orexin-1 (OX1R) and orexin-2 (OX2R) receptors, various dual OX1/2R antagonists have been shown to promote sleep in animals and humans. While selective blockade of OX2R seems to be sufficient to initiate and prolong sleep, the beneficial effect of additional inhibition of OX1R remains controversial. The relative contribution of OX1R and OX2R to the sleep effects induced by a dual OX1/2R antagonist was further investigated in the rat, and specifically on rapid eye movement (REM) sleep since a deficiency of the orexin system is associated with narcolepsy/cataplexy based on clinical and pre-clinical data. As expected, the dual OX1/2R antagonist SB-649868 was effective in promoting non-REM (NREM) and REM sleep following oral dosing (10 and 30 mg/kg) at the onset of the dark phase. However, a disruption of REM sleep was evidenced by a more pronounced reduction in the onset of REM as compared to NREM sleep, a marked enhancement of the REM/total sleep ratio, and the occurrence of a few episodes of direct wake to REM sleep transitions (REM intrusion). When administered subcutaneously, the OX2R antagonist JNJ-10397049 (10 mg/kg) increased NREM duration whereas the OX1R antagonist GSK-1059865 (10 mg/kg) did not alter sleep. REM sleep was not affected either by OX2R or OX1R blockade alone, but administration of the OX1R antagonist in combination with the OX2R antagonist induced a significant reduction in REM sleep latency and an increase in REM sleep duration at the expense of the time spent in NREM sleep. These results indicate that additional blockade of OX1R to OX2R antagonism elicits a dysregulation of REM sleep by shifting the balance in favor of REM sleep at the expense of NREM sleep that may increase the risk of adverse events. Translation of this hypothesis remains to be tested in the clinic. PMID:24592208

  10. Multi-gene epigenetic silencing of tumor suppressor genes in T-cell lymphoma cells; delayed expression of the p16 protein upon reversal of the silencing

    DEFF Research Database (Denmark)

    Nagasawa, T; Zhang, Q; Raghunath, P N; Wong, H Y; El-Salem, M; Szallasi, A; Marzec, M; Gimotty, P; Rook, A H; Vonderheid, E C; Odum, Niels; Wasik, M A

    2006-01-01

    To understand better T-cell lymphomagenesis, we examined promoter CpG methylation and mRNA expression of closely related genes encoding p16, p15, and p14 tumor suppressor genes in cultured malignant T-cells that were derived from cutaneous, adult type, and anaplastic lymphoma kinase (ALK)-express......To understand better T-cell lymphomagenesis, we examined promoter CpG methylation and mRNA expression of closely related genes encoding p16, p15, and p14 tumor suppressor genes in cultured malignant T-cells that were derived from cutaneous, adult type, and anaplastic lymphoma kinase (ALK......)-expressing T-cell lymphomas. p16 gene was epigenetically silenced in all but one of the 10 malignant T-cell lines examined, p15 gene silenced in roughly half of the lines, and p14 was the least frequently affected. Extensive methylation of the p16 promoter was seen in six out of 10 cutaneous T-cell lymphoma...... patient samples and corresponded with lack of p16 protein expression in the cases examined. Treatment of cultured T-cells with the DNA methyltransferase inhibitor, 5-aza-2-deoxy-cytidine, resulted in reversal of the p16 gene silencing. However, expression of p16 protein was delayed in relationship to p16...

  11. Host-induced gene silencing: a tool for understanding fungal host interaction and for developing novel disease control strategies.

    Science.gov (United States)

    Nunes, Cristiano C; Dean, Ralph A

    2012-06-01

    Recent discoveries regarding small RNAs and the mechanisms of gene silencing are providing new opportunities to explore fungal pathogen-host interactions and potential strategies for novel disease control. Plant pathogenic fungi are a constant and major threat to global food security; they represent the largest group of disease-causing agents on crop plants on the planet. An initial understanding of RNA silencing mechanisms and small RNAs was derived from model fungi. Now, new knowledge with practical implications for RNA silencing is beginning to emerge from the study of plant-fungus interactions. Recent studies have shown that the expression of silencing constructs in plants designed on fungal genes can specifically silence their targets in invading pathogenic fungi, such as Fusarium verticillioides, Blumeria graminis and Puccinia striiformis f.sp. tritici. Here, we highlight the important general aspects of RNA silencing mechanisms and emphasize recent findings from plant pathogenic fungi. Strategies to employ RNA silencing to investigate the basis of fungal pathogenesis are discussed. Finally, we address important aspects for the development of fungal-derived resistance through the expression of silencing constructs in host plants as a powerful strategy to control fungal disease. PMID:22111693

  12. Uudised : Rannap sai raha lõpuks kätte. No Big Silence esitleb uut heliplaati

    Index Scriptorium Estoniae

    2000-01-01

    Pärnus toimunud lühima öö laulukonkursil võitis peaauhinna R. Rannap. Ans. No-Big-Silence on soojendusbändiks 2. juulil Tallinna Lauluväljakul toimuval Iron Maideni kontserdil. Ans. No-Big-Silence esitleb oma uut heliplaati "successful, bitch and beautiful"

  13. piRNA-guided slicing of transposon transcripts enforces their transcriptional silencing via specifying the nuclear piRNA repertoire

    OpenAIRE

    Senti, Kirsten-André; Jurczak, Daniel; Sachidanandam, Ravi; Brennecke, Julius

    2015-01-01

    In this study, Senti et al investigate how cytoplasmic post-transcriptional silencing influences transcriptional silencing in the nucleus. They show that Piwi-bound piRNA populations depend almost exclusively on prior piRNA-guided transcript slicing, thus providing further insight into the regulation of piRNA biogenesis in the developing Drosophila ovary.

  14. Triticum mosaic poacevirus enlists P1 rather than HC-Pro to suppress RNA silencing-mediated host defense

    Science.gov (United States)

    RNA silencing, or posttranscriptional gene silencing (PTGS) is one of the most important defense mechanisms employed by higher plants and animals to defend against viral infections. Plant viruses evolved by adopting divergent proteins, even within single virus families, to counter this host defense ...

  15. Analysis of the siRNA-mediated gene silencing process targeting three homologous genes controlling soybean seed oil quality

    Science.gov (United States)

    Since the discovery of RNA silencing in the nineties, the implication and potential application of this new technology have been recognized. In the past decades, RNA silencing has gained significant attention because its success in genomic scale research and also in the genetic improvement of crop p...

  16. Transcriptional provirus silencing as a crosstalk of de novo DNA methylation and epigenomic features at the integration site.

    Science.gov (United States)

    Senigl, Filip; Auxt, Miroslav; Hejnar, Jirí

    2012-07-01

    The autonomous transcription of integrated retroviruses strongly depends on genetic and epigenetic effects of the chromatin at the site of integration. These effects are mostly suppressive and proviral activity can be finally silenced by mechanisms, such as DNA methylation and histone modifications. To address the role of the integration site at the whole-genome-scale, we performed clonal analysis of provirus silencing with an avian leucosis/sarcoma virus-based reporter vector and correlated the transcriptional silencing with the epigenomic landscape of respective integrations. We demonstrate efficient provirus silencing in human HCT116 cell line, which is strongly but not absolutely dependent on the de novo DNA methyltransferase activity, particularly of Dnmt3b. Proviruses integrated close to the transcription start sites of active genes into the regions enriched in H3K4 trimethylation display long-term stability of expression and are resistant to the transcriptional silencing after over-expression of Dnmt3a or Dnmt3b. In contrast, proviruses in the intergenic regions tend to spontaneous transcriptional silencing even in Dnmt3a(-/-) Dnmt3b(-/-) cells. The silencing of proviruses within genes is accompanied with DNA methylation of long terminal repeats, whereas silencing in intergenic regions is DNA methylation-independent. These findings indicate that the epigenomic features of integration sites are crucial for their permissivity to the proviral expression. PMID:22379139

  17. The influenza A virus NS1 protein binds small interfering RNAs and suppresses RNA silencing in plants

    NARCIS (Netherlands)

    Bucher, E.C.; Hemmes, J.C.; Haan, de P.; Goldbach, R.W.; Prins, M.W.

    2004-01-01

    RNA silencing comprises a set of sequence-specific RNA degradation pathways that occur in a wide range of eukaryotes, including animals, fungi and plants. A hallmark of RNA silencing is the presence of small interfering RNA molecules (siRNAs). The siRNAs are generated by cleavage of larger double-st

  18. The yeast SAS (something about silencing) protein complex contains a MYST-type putative acetyltransferase and functions with chromatin assembly factor ASF1

    OpenAIRE

    Osada, Shigehiro; Sutton, Ann; Muster, Nemone; Brown, Christine E.; Yates, John R.; Sternglanz, Rolf; Workman, Jerry L.

    2001-01-01

    It is well established that acetylation of histone and nonhistone proteins is intimately linked to transcriptional activation. However, loss of acetyltransferase activity has also been shown to cause silencing defects, implicating acetylation in gene silencing. The something about silencing (Sas) 2 protein of Saccharomyces cerevisiae, a member of the MYST (MOZ, Ybf2/Sas3, Sas2, and TIP60) acetyltransferase family, promotes silencing at HML and telomeres. Here we identify a ∼450-kD SAS complex...

  19. Displacement of Pathogens by an Engineered Bacterium Is a Multifactorial Process That Depends on Attachment Competition and Interspecific Antagonism.

    Science.gov (United States)

    Al-Saedi, Fitua; Stones, Daniel Henry; Vaz, Diana Pereira; Krachler, Anne Marie

    2016-06-01

    Pathogen attachment to host cells is a key process during infection, and inhibition of pathogen adhesion is a promising approach to the prevention of infectious disease. We have previously shown that multivalent adhesion molecules (MAMs) are abundant in both pathogenic and commensal bacterial species, mediate early attachment to host cells, and can contribute to virulence. Here, we investigated the efficacy of an engineered bacterium expressing a commensal MAM on its surface in preventing pathogen attachment and pathogen-mediated cytotoxicity in a tissue culture infection model. We were able to dissect the individual contributions of adhesion and interspecific antagonism on the overall outcome of infection for a range of different pathogens by comparison with the results obtained with a fully synthetic adhesion inhibitor. We found that the potential of the engineered bacterium to outcompete the pathogen is not always solely dependent on its ability to hinder host attachment but, depending on the pathogenic species, may also include elements of interspecific antagonism, such as competition for nutrients and its ability to cause a loss of fitness due to production of antimicrobial factors. PMID:27001540

  20. Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal Farnesoid X Receptor (FXR) Antagonists: Molecular Basis of FXR Antagonism.

    Science.gov (United States)

    Huang, Huang; Si, Pei; Wang, Lei; Xu, Yong; Xu, Xin; Zhu, Jin; Jiang, Hualiang; Li, Weihua; Chen, Lili; Li, Jian

    2015-07-01

    Farnesoid X receptor (FXR) plays an important role in the regulation of cholesterol, lipid, and glucose metabolism. Recently, several studies on the molecular basis of FXR antagonism have been reported. However, none of these studies employs an FXR antagonist with nonsteroidal scaffold. On the basis of our previously reported FXR antagonist with a trisubstituted isoxazole scaffold, a novel nonsteroidal FXR ligand was designed and used as a lead for structural modification. In total, 39 new trisubstituted isoxazole derivatives were designed and synthesized, which led to pharmacological profiles ranging from agonist to antagonist toward FXR. Notably, compound 5s (4'-[(3-{[3-(2-chlorophenyl)-5-(2-thienyl)isoxazol-4-yl]methoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid), containing a thienyl-substituted isoxazole ring, displayed the best antagonistic activity against FXR with good cellular potency (IC50 =12.2 ± 0.2 μM). Eventually, this compound was used as a probe in a molecular dynamics simulation assay. Our results allowed us to propose an essential molecular basis for FXR antagonism, which is consistent with a previously reported antagonistic mechanism; furthermore, E467 on H12 was found to be a hot-spot residue and may be important for the future design of nonsteroidal antagonists of FXR. PMID:25982493